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Tutorials Book on Deep Chem

Deep chem tutorial

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Tutorials Book on Deep Chem

Deep chem tutorial

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Deep Forest Publishing Deep Forest Publishing

DeepChem
The DeepChem Book
The DeepChem Book is a step-by-step tutorial series for deep
life sciences. The author, Bharath Ramsundar and the
DeepChem team, cover the essential tools and techniques for
mastering deep learning in life sciences. Tailored for
beginners in both machine learning and life sciences, the

The
book builds a repertoire of tools required to perform
meaningful work in the dynamic field of life sciences. Going
beyond machine learning, the tutorial covers critical aspects

DeepChem
of data handling necessary for constructing systems within
the deep life sciences. Executed on Google Colab, these
tutorials prioritize accessibility and convenience, providing
an open avenue for exploration.
Book
“The DeepChem project aims to make high quality open source
software for scientific machine learning more accessible to
scientists and developers worldwide. We have a particular Democratizing Deep Learning
for Sciences
focus on molecular machine learning and drug discovery, but
also support a broad range of applications in bioinformatics,
materials science, and computational physics. I started
DeepChem while doing my Ph.D. at Stanford, but today
DeepChem operates as a global distributed community of Ramsundar
researchers spread across many academic and industrial
institutions. We hope that you will join our community and
help us build!”
Bharath
- Bharath Ramsundar

www.deepchem.io
www.deepforestsci.com Bharath Ramsundar and the DeepChem Team
The DeepChem Book
Democratizing Deep-Learning for Drug Discovery Quantum Chemistry,
Materials Science and Biology

Bharath Ramsundar and the DeepChem Community

Acknowledgement
We acknowledge the DeepChem community for their contributions and support.
Contents
1. Introduction To Deepchem
1. The Basic Tools of the Deep Life Sciences
2. Working With Datasets
3. An Introduction To MoleculeNet
4. Molecular Fingerprints
5. Creating Models with TensorFlow and PyTorch
6. Introduction to Graph Convolutions
7. Going Deeper on Molecular Featurizations
8. Working With Splitters
9. Advanced Model Training
10. Creating a high fidelity model from experimental data
11. Putting Multitask Learning to Work
12. Modeling Protein Ligand Interactions
13. Modeling Protein Ligand Interactions With Atomic Convolutions
14. Conditional Generative Adversarial Networks
15. Training a Generative Adversarial Network on MNIST
16. Advanced model training using hyperopt
17. Introduction to Gaussian Processes
18. PytorchLightning Integration

2. Molecular Machine Learning

1. Molecular Fingerprints
2. Going Deeper on Molecular Featurizations
3. Learning Unsupervised Embeddings for Molecules
4. Atomic Contributions for Molecules
5. Interactive Model Evaluation with Trident Chemwidgets
6. Transfer Learning With ChemBERTa Transformers
7. Training a Normalizing Flow on QM9
8. Large Scale Chemical Screens
9. Introduction to Molecular Attention Transformer
10. Generating molecules with MolGAN
11. Introduction to GROVER

3. Modeling Proteins
1. Protein Deep Learning

4. Protein Ligand Modeling

1. Modeling Protein Ligand Interactions
2. Modeling Protein Ligand Interactions With Atomic Convolutions
3. DeepChemXAlphafold

5. Quantum Chemistry
1. Exploring Quantum Chemistry with GDB1k
2. DeepQMC tutorial
3. Training an Exchange Correlation Functional using Deepchem
6. Bioinformatics
1. Introduction to Bioinformatics
2. Multisequence Alignments
3. Deep probabilistic analysis of single-cell omics data

7. Material Sciences
1. Introduction To Material Science

8. Machine Learning Methods

1. Using Reinforcement Learning to Play Pong
2. Introduction to Model Interpretability
3. Uncertainty In Deep Learning

9. Deep Differential Equations

1. Physics Informed Neural Networks
2. Introducing JaxModel and PINNModel
3. About Neural ODE : Using Torchdiffeq with Deepchem

10. Equivariance
1. Introduction to Equivariance
2. Modeling Protein Ligand Interactions With Atomic Convolutions
3. DeepChemXAlphafold

11. Olfaction
1. Predict Multi Label Odor Descriptors using OpenPOM
The Basic Tools of the Deep Life Sciences
Welcome to DeepChem's introductory tutorial for the deep life sciences. This series of notebooks is a step-by-step guide
for you to get to know the new tools and techniques needed to do deep learning for the life sciences. We'll start from
the basics, assuming that you're new to machine learning and the life sciences, and build up a repertoire of tools and
techniques that you can use to do meaningful work in the life sciences.

Scope: This tutorial will encompass both the machine learning and data handling needed to build systems for the deep
life sciences.

Colab
This tutorial and the rest in the sequences are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Why do the DeepChem Tutorial?

1) Career Advancement: Applying AI in the life sciences is a booming industry at present. There are a host of newly
funded startups and initiatives at large pharmaceutical and biotech companies centered around AI. Learning and
mastering DeepChem will bring you to the forefront of this field and will prepare you to enter a career in this field.

2) Humanitarian Considerations: Disease is the oldest cause of human suffering. From the dawn of human
civilization, humans have suffered from pathogens, cancers, and neurological conditions. One of the greatest
achievements of the last few centuries has been the development of effective treatments for many diseases. By
mastering the skills in this tutorial, you will be able to stand on the shoulders of the giants of the past to help develop
new medicine.

3) Lowering the Cost of Medicine: The art of developing new medicine is currently an elite skill that can only be
practiced by a small core of expert practitioners. By enabling the growth of open source tools for drug discovery, you
can help democratize these skills and open up drug discovery to more competition. Increased competition can help
drive down the cost of medicine.

Getting Extra Credit

If you're excited about DeepChem and want to get more involved, there are some things that you can do right now:

Star DeepChem on GitHub! - https://github.com/deepchem/deepchem

Join the DeepChem forums and introduce yourself! - https://forum.deepchem.io
Say hi on the DeepChem gitter - https://gitter.im/deepchem/Lobby
Make a YouTube video teaching the contents of this notebook.

Prerequisites
This tutorial sequence will assume some basic familiarity with the Python data science ecosystem. We will assume that
you have familiarity with libraries such as Numpy, Pandas, and TensorFlow. We'll provide some brief refreshers on
basics through the tutorial so don't worry if you're not an expert.

Setup
The first step is to get DeepChem up and running. We recommend using Google Colab to work through this tutorial
series. You'll also need to run the following commands to get DeepChem installed on your colab notebook. We are going
to use a model based on tensorflow, because of that we've added [tensorflow] to the pip install command to ensure the
necessary dependencies are also installed

!pip install --pre deepchem[tensorflow]

You can of course run this tutorial locally if you prefer. In this case, don't run the above cell since it will download and
install Anaconda on your local machine. In either case, we can now import the deepchem package to play with.

import deepchem as dc
dc.__version__
'2.5.0.dev'

Training a Model with DeepChem: A First Example

Deep learning can be used to solve many sorts of problems, but the basic workflow is usually the same. Here are the
typical steps you follow.

1. Select the data set you will train your model on (or create a new data set if there isn't an existing suitable one).
2. Create the model.
3. Train the model on the data.
4. Evaluate the model on an independent test set to see how well it works.
5. Use the model to make predictions about new data.

With DeepChem, each of these steps can be as little as one or two lines of Python code. In this tutorial we will walk
through a basic example showing the complete workflow to solve a real world scientific problem.

The problem we will solve is predicting the solubility of small molecules given their chemical formulas. This is a very
important property in drug development: if a proposed drug isn't soluble enough, you probably won't be able to get
enough into the patient's bloodstream to have a therapeutic effect. The first thing we need is a data set of measured
solubilities for real molecules. One of the core components of DeepChem is MoleculeNet, a diverse collection of chemical
and molecular data sets. For this tutorial, we can use the Delaney solubility data set. The property of solubility in this
data set is reported in log(solubility) where solubility is measured in moles/liter.

tasks, datasets, transformers = dc.molnet.load_delaney(featurizer='GraphConv')

train_dataset, valid_dataset, test_dataset = datasets

I won't say too much about this code right now. We will see many similar examples in later tutorials. There are two
details I do want to draw your attention to. First, notice the featurizer argument passed to the load_delaney()
function. Molecules can be represented in many ways. We therefore tell it which representation we want to use, or in
more technical language, how to "featurize" the data. Second, notice that we actually get three different data sets: a
training set, a validation set, and a test set. Each of these serves a different function in the standard deep learning
workflow.

Now that we have our data, the next step is to create a model. We will use a particular kind of model called a "graph
convolutional network", or "graphconv" for short.

model = dc.models.GraphConvModel(n_tasks=1, mode='regression', dropout=0.2,batch_normalize=False)

Here again I will not say much about the code. Later tutorials will give lots more information about GraphConvModel , as
well as other types of models provided by DeepChem.

We now need to train the model on the data set. We simply give it the data set and tell it how many epochs of training
to perform (that is, how many complete passes through the data to make).

model.fit(train_dataset, nb_epoch=100)

If everything has gone well, we should now have a fully trained model! But do we? To find out, we must evaluate the
model on the test set. We do that by selecting an evaluation metric and calling evaluate() on the model. For this
example, let's use the Pearson correlation, also known as r2, as our metric. We can evaluate it on both the training set
and test set.

metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)
print("Training set score:", model.evaluate(train_dataset, [metric], transformers))
print("Test set score:", model.evaluate(test_dataset, [metric], transformers))

Training set score: {'pearson_r2_score': 0.9323622956442351}

Test set score: {'pearson_r2_score': 0.6898768897014962}

Notice that it has a higher score on the training set than the test set. Models usually perform better on the particular
data they were trained on than they do on similar but independent data. This is called "overfitting", and it is the reason
it is essential to evaluate your model on an independent test set.

Our model still has quite respectable performance on the test set. For comparison, a model that produced totally
random outputs would have a correlation of 0, while one that made perfect predictions would have a correlation of 1.
Our model does quite well, so now we can use it to make predictions about other molecules we care about.

Since this is just a tutorial and we don't have any other molecules we specifically want to predict, let's just use the first
ten molecules from the test set. For each one we print out the chemical structure (represented as a SMILES string) and
the predicted log(solubility). To put these predictions in context, we print out the log(solubility) values from the test set
as well.

solubilities = model.predict_on_batch(test_dataset.X[:10])
for molecule, solubility, test_solubility in zip(test_dataset.ids, solubilities, test_dataset.y):
print(solubility, test_solubility, molecule)

[-1.8629359] [-1.60114461] c1cc2ccc3cccc4ccc(c1)c2c34

[0.6617248] [0.20848251] Cc1cc(=O)[nH]c(=S)[nH]1
[-0.5705674] [-0.01602738] Oc1ccc(cc1)C2(OC(=O)c3ccccc23)c4ccc(O)cc4
[-2.0929456] [-2.82191713] c1ccc2c(c1)cc3ccc4cccc5ccc2c3c45
[-1.4962314] [-0.52891635] C1=Cc2cccc3cccc1c23
[1.8620405] [1.10168349] CC1CO1
[-0.5858227] [-0.88987406] CCN2c1ccccc1N(C)C(=S)c3cccnc23
[-0.9799993] [-0.52649706] CC12CCC3C(CCc4cc(O)ccc34)C2CCC1=O
[-1.0176951] [-0.76358725] Cn2cc(c1ccccc1)c(=O)c(c2)c3cccc(c3)C(F)(F)F
[0.05622783] [-0.64020358] ClC(Cl)(Cl)C(NC=O)N1C=CN(C=C1)C(NC=O)C(Cl)(Cl)Cl

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro1,
title={The Basic Tools of the Deep Life Sciences},
organization={DeepChem},
author={Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/The_Basic_Tools_of_the_Deep
year={2021},
}
Working With Datasets
Data is central to machine learning. This tutorial introduces the Dataset class that DeepChem uses to store and
manage data. It provides simple but powerful tools for efficiently working with large amounts of data. It also is designed
to easily interact with other popular Python frameworks such as NumPy, Pandas, TensorFlow, and PyTorch.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

We can now import the deepchem package to play with.

import deepchem as dc
dc.__version__

'2.4.0-rc1.dev'

Anatomy of a Dataset
In the last tutorial we loaded the Delaney dataset of molecular solubilities. Let's load it again.

tasks, datasets, transformers = dc.molnet.load_delaney(featurizer='GraphConv')

train_dataset, valid_dataset, test_dataset = datasets

We now have three Dataset objects: the training, validation, and test sets. What information does each of them contain?
We can start to get an idea by printing out the string representation of one of them.

print(test_dataset)

There's a lot of information there, so let's start at the beginning. It begins with the label "DiskDataset". Dataset is an
abstract class. It has a few subclasses that correspond to different ways of storing data.

DiskDataset is a dataset that has been saved to disk. The data is stored in a way that can be efficiently accessed,
even if the total amount of data is far larger than your computer's memory.
NumpyDataset is an in-memory dataset that holds all the data in NumPy arrays. It is a useful tool when
manipulating small to medium sized datasets that can fit entirely in memory.
ImageDataset is a more specialized class that stores some or all of the data in image files on disk. It is useful when
working with models that have images as their inputs or outputs.

Now let's consider the contents of the Dataset. Every Dataset stores a list of samples. Very roughly speaking, a sample
is a single data point. In this case, each sample is a molecule. In other datasets a sample might correspond to an
experimental assay, a cell line, an image, or many other things. For every sample the dataset stores the following
information.

The features, referred to as X . This is the input that should be fed into a model to represent the sample.
The labels, referred to as y . This is the desired output from the model. During training, it tries to make the model's
output for each sample as close as possible to y .
The weights, referred to as w . This can be used to indicate that some data values are more important than others.
In later tutorials we will see examples of how this is useful.
An ID, which is a unique identifier for the sample. This can be anything as long as it is unique. Sometimes it is just
an integer index, but in this dataset the ID is a SMILES string describing the molecule.

Notice that X , y , and w all have 113 as the size of their first dimension. That means this dataset contains 113
samples.

The final piece of information listed in the output is task_names . Some datasets contain multiple pieces of information
for each sample. For example, if a sample represents a molecule, the dataset might record the results of several
different experiments on that molecule. This dataset has only a single task: "measured log solubility in mols per litre".
Also notice that y and w each have shape (113, 1). The second dimension of these arrays usually matches the
number of tasks.

Accessing Data from a Dataset

There are many ways to access the data contained in a dataset. The simplest is just to directly access the X , y , w ,
and ids properties. Each of these returns the corresponding information as a NumPy array.

test_dataset.y

array([[-1.7065408738415053],
[0.2911162036252904],
[-1.4272475857596547],
[-0.9254664241210759],
[-1.9526976701170347],
[1.3514839414275706],
[-0.8591934405084332],
[-0.6509069205829855],
[-0.32900957160729316],
[0.6082797680572224],
[1.8295961803473488],
[1.6213096604219008],
[1.3751528641463715],
[0.45632528420252055],
[1.0532555151706793],
[-1.1053502367839627],
[-0.2011973889257683],
[0.3479216181504126],
[-0.9870056231899582],
[-0.8161160011602158],
[0.8402352107014712],
[0.22815686919328],
[0.06247441016167367],
[1.040947675356903],
[-0.5197810887208284],
[0.8023649343513898],
[-0.41895147793873655],
[-2.5964923680684198],
[1.7443880585596654],
[0.45206487811313645],
[0.233837410645792],
[-1.7917489956291888],
[0.7739622270888287],
[1.0011838851893173],
[-0.05445006806920272],
[1.1043803882432892],
[0.7597608734575482],
[-0.7001382798380905],
[0.8213000725264304],
[-1.3136367567094103],
[0.4567986626568967],
[-0.5732728540653187],
[0.4094608172192949],
[-0.3242757870635329],
[-0.049716283525442634],
[-0.39054877067617544],
[-0.08095926151425996],
[-0.2627365879946506],
[-0.5467636606202616],
[1.997172153196459],
[-0.03551492989416198],
[1.4508934168465344],
[-0.8639272250521937],
[0.23904457364392848],
[0.5278054308132993],
[-0.48475108309700315],
[0.2248432200126478],
[0.3431878336066523],
[1.5029650468278963],
[-0.4946920306388995],
[0.3479216181504126],
[0.7928973652638694],
[0.5609419226196206],
[-0.13965818985688602],
[-0.13965818985688602],
[0.15857023640000523],
[1.6071083067906202],
[1.9006029485037514],
[-0.7171799041956278],
[-0.8165893796145915],
[-0.13019062076936566],
[-0.24380144981960986],
[-0.14912575894440638],
[0.9538460397517154],
[-0.07811899078800374],
[-0.18226225075072758],
[0.2532459272752089],
[0.6887541053011454],
[0.044012650441008896],
[-0.5514974451640217],
[-0.2580028034508905],
[-0.021313576262881533],
[-2.4128215277705247],
[0.07336211461232214],
[0.9017744097703536],
[1.9384732248538328],
[0.8402352107014712],
[-0.10652169805056463],
[1.07692443788948],
[-0.403803367398704],
[1.2662758196398873],
[-0.2532690189071302],
[0.29064282517091444],
[0.9443784706641951],
[-0.41563782875810434],
[-0.7370617992794205],
[-1.0012069768212388],
[0.46626623174441706],
[0.3758509469585975],
[-0.46628932337633816],
[1.2662758196398873],
[-1.4968342185529295],
[-0.17800184466134344],
[0.8828392715953128],
[-0.6083028596891439],
[-2.170451759130003],
[0.32898647997537184],
[0.3005837727128107],
[0.6461500444073038],
[1.5058053175541524],
[-0.007585601085977053],
[-0.049716283525442634],
[-0.6849901692980588]], dtype=object)

This is a very easy way to access data, but you should be very careful about using it. This requires the data for all
samples to be loaded into memory at once. That's fine for small datasets like this one, but for large datasets it could
easily take more memory than you have.

A better approach is to iterate over the dataset. That lets it load just a little data at a time, process it, then free the
memory before loading the next bit. You can use the itersamples() method to iterate over samples one at a time.

for X, y, w, id in test_dataset.itersamples():
print(y, id)

[-1.70654087] C1c2ccccc2c3ccc4ccccc4c13
[0.2911162] COc1ccccc1Cl
[-1.42724759] COP(=S)(OC)Oc1cc(Cl)c(Br)cc1Cl
[-0.92546642] ClC(Cl)CC(=O)NC2=C(Cl)C(=O)c1ccccc1C2=O
[-1.95269767] ClC(Cl)C(c1ccc(Cl)cc1)c2ccc(Cl)cc2
[1.35148394] COC(=O)C=C
[-0.85919344] CN(C)C(=O)Nc2ccc(Oc1ccc(Cl)cc1)cc2
[-0.65090692] N(=Nc1ccccc1)c2ccccc2
[-0.32900957] CC(C)c1ccc(C)cc1
[0.60827977] Oc1c(Cl)cccc1Cl
[1.82959618] OCC2OC(OC1(CO)OC(CO)C(O)C1O)C(O)C(O)C2O
[1.62130966] OC1C(O)C(O)C(O)C(O)C1O
[1.37515286] Cn2c(=O)n(C)c1ncn(CC(O)CO)c1c2=O
[0.45632528] OCC(NC(=O)C(Cl)Cl)C(O)c1ccc(cc1)N(=O)=O
[1.05325552] CCC(O)(CC)CC
[-1.10535024] CC45CCC2C(CCC3CC1SC1CC23C)C4CCC5O
[-0.20119739] Brc1ccccc1Br
[0.34792162] Oc1c(Cl)cc(Cl)cc1Cl
[-0.98700562] CCCN(CCC)c1c(cc(cc1N(=O)=O)S(N)(=O)=O)N(=O)=O
[-0.816116] C2c1ccccc1N(CCF)C(=O)c3ccccc23
[0.84023521] CC(C)C(=O)C(C)C
[0.22815687] O=C1NC(=O)NC(=O)C1(C(C)C)CC=C(C)C
[0.06247441] c1c(O)C2C(=O)C3cc(O)ccC3OC2cc1(OC)
[1.04094768] Cn1cnc2n(C)c(=O)n(C)c(=O)c12
[-0.51978109] CC(=O)SC4CC1=CC(=O)CCC1(C)C5CCC2(C)C(CCC23CCC(=O)O3)C45
[0.80236493] Cc1ccc(O)cc1C
[-0.41895148] O(c1ccccc1)c2ccccc2
[-2.59649237] Clc1cc(Cl)c(cc1Cl)c2cc(Cl)c(Cl)cc2Cl
[1.74438806] NC(=O)c1cccnc1
[0.45206488] Sc1ccccc1
[0.23383741] CNC(=O)Oc1cc(C)cc(C)c1
[-1.791749] ClC1CC2C(C1Cl)C3(Cl)C(=C(Cl)C2(Cl)C3(Cl)Cl)Cl
[0.77396223] CSSC
[1.00118389] NC(=O)c1ccccc1
[-0.05445007] Clc1ccccc1Br
[1.10438039] COC(=O)c1ccccc1OC2OC(COC3OCC(O)C(O)C3O)C(O)C(O)C2O
[0.75976087] CCCCC(O)CC
[-0.70013828] CCN2c1nc(C)cc(C)c1NC(=O)c3cccnc23
[0.82130007] Oc1cc(Cl)cc(Cl)c1
[-1.31363676] Cc1cccc2c1ccc3ccccc32
[0.45679866] CCCCC(CC)CO
[-0.57327285] CC(C)N(C(C)C)C(=O)SCC(=CCl)Cl
[0.40946082] Cc1ccccc1
[-0.32427579] Clc1cccc(n1)C(Cl)(Cl)Cl
[-0.04971628] C1CCC=CCC1
[-0.39054877] CN(C)C(=S)SSC(=S)N(C)C
[-0.08095926] COC1=CC(=O)CC(C)C13Oc2c(Cl)c(OC)cc(OC)c2C3=O
[-0.26273659] CCCCCCCCCCO
[-0.54676366] CCC(C)(C)CC
[1.99717215] CNC(=O)C(C)SCCSP(=O)(OC)(OC)
[-0.03551493] Oc1cc(Cl)c(Cl)c(Cl)c1Cl
[1.45089342] CCCC=O
[-0.86392723] CC4CC3C2CCC1=CC(=O)C=CC1(C)C2(F)C(O)CC3(C)C4(O)C(=O)COC(C)=O
[0.23904457] CCCC
[0.52780543] COc1ccccc1O
[-0.48475108] CC1CC2C3CCC(O)(C(=O)C)C3(C)CC(O)C2(F)C4(C)C=CC(=O)C=C14
[0.22484322] ClC(Cl)C(Cl)(Cl)Cl
[0.34318783] CCOC(=O)c1ccccc1C(=O)OCC
[1.50296505] CC(C)CO
[-0.49469203] CC(C)Cc1ccccc1
[0.34792162] ICI
[0.79289737] CCCC(O)CCC
[0.56094192] CCCCCOC(=O)C
[-0.13965819] Oc1c(Cl)c(Cl)cc(Cl)c1Cl
[-0.13965819] CCCc1ccccc1
[0.15857024] FC(F)(Cl)C(F)(F)Cl
[1.60710831] CC=CC=O
[1.90060295] CN(C)C(=O)N(C)C
[-0.7171799] Cc1cc(C)c(C)cc1C
[-0.81658938] CC(=O)OC3(CCC4C2CCC1=CC(=O)CCC1C2CCC34C)C#C
[-0.13019062] CCOP(=S)(OCC)N2C(=O)c1ccccc1C2=O
[-0.24380145] c1ccccc1NC(=O)c2c(O)cccc2
[-0.14912576] CCN(CC)C(=S)SCC(Cl)=C
[0.95384604] ClCC
[-0.07811899] CC(=O)Nc1cc(NS(=O)(=O)C(F)(F)F)c(C)cc1C
[-0.18226225] O=C(C=CC=Cc2ccc1OCOc1c2)N3CCCCC3
[0.25324593] CC/C=C\C
[0.68875411] CNC(=O)ON=C(CSC)C(C)(C)C
[0.04401265] O=C2NC(=O)C1(CCCCCCC1)C(=O)N2
[-0.55149745] c1(C(C)(C)C)cc(C(C)(C)C)cc(OC(=O)NC)c1
[-0.2580028] Oc2cc(O)c1C(=O)CC(Oc1c2)c3ccc(O)c(O)c3
[-0.02131358] O=C(c1ccccc1)c2ccccc2
[-2.41282153] CCCCCCCCCCCCCCCCCCCC
[0.07336211] N(Nc1ccccc1)c2ccccc2
[0.90177441] CCC(CC)CO
[1.93847322] Oc1ccncc1
[0.84023521] Cl\C=C/Cl
[-0.1065217] CC1CCCC1
[1.07692444] CC(C)CC(C)O
[-0.40380337] O2c1ccc(N)cc1N(C)C(=O)c3cc(C)ccc23
[1.26627582] CC(C)(C)CO
[-0.25326902] CC(C)(C)C(=O)C(Oc1ccc(Cl)cc1)n2cncn2
[0.29064283] Cc1cc(no1)C(=O)NNCc2ccccc2
[0.94437847] CC=C
[-0.41563783] Oc1ccc(Cl)cc1Cc2cc(Cl)ccc2O
[-0.7370618] CCOC(=O)Nc2cccc(OC(=O)Nc1ccccc1)c2
[-1.00120698] O=C1c2ccccc2C(=O)c3ccccc13
[0.46626623] CCCCCCC(C)O
[0.37585095] CC1=C(C(=O)Nc2ccccc2)S(=O)(=O)CCO1
[-0.46628932] CCCCc1ccccc1
[1.26627582] O=C1NC(=O)C(=O)N1
[-1.49683422] COP(=S)(OC)Oc1ccc(Sc2ccc(OP(=S)(OC)OC)cc2)cc1
[-0.17800184] NS(=O)(=O)c1cc(ccc1Cl)C2(O)NC(=O)c3ccccc23
[0.88283927] CC(C)COC(=O)C
[-0.60830286] CC(C)C(C)(C)C
[-2.17045176] Clc1ccc(c(Cl)c1Cl)c2c(Cl)cc(Cl)c(Cl)c2Cl
[0.32898648] N#Cc1ccccc1C#N
[0.30058377] Cc1cccc(c1)N(=O)=O
[0.64615004] FC(F)(F)C(Cl)Br
[1.50580532] CNC(=O)ON=C(SC)C(=O)N(C)C
[-0.0075856] CCSCCSP(=S)(OC)OC
[-0.04971628] CCC(C)C
[-0.68499017] COP(=O)(OC)OC(=CCl)c1cc(Cl)c(Cl)cc1Cl

Most deep learning models can process a batch of multiple samples all at once. You can use iterbatches() to iterate
over batches of samples.

for X, y, w, ids in test_dataset.iterbatches(batch_size=50):

print(y.shape)

(50, 1)
(50, 1)
(13, 1)

iterbatches() has other features that are useful when training models. For example,
iterbatches(batch_size=100, epochs=10, deterministic=False) will iterate over the complete dataset ten
times, each time with the samples in a different random order.

Datasets can also expose data using the standard interfaces for TensorFlow and PyTorch. To get a
tensorflow.data.Dataset , call make_tf_dataset() . To get a torch.utils.data.IterableDataset , call
make_pytorch_dataset() . See the API documentation for more details.

The final way of accessing data is to_dataframe() . This copies the data into a Pandas DataFrame . This requires
storing all the data in memory at once, so you should only use it with small datasets.

test_dataset.to_dataframe()

X y w ids

0 <deepchem.feat.mol_graphs.ConvMol object at 0x... -1.706541 1.0 C1c2ccccc2c3ccc4ccccc4c13

1 <deepchem.feat.mol_graphs.ConvMol object at 0x... 0.291116 1.0 COc1ccccc1Cl

2 <deepchem.feat.mol_graphs.ConvMol object at 0x... -1.427248 1.0 COP(=S)(OC)Oc1cc(Cl)c(Br)cc1Cl

3 <deepchem.feat.mol_graphs.ConvMol object at 0x... -0.925466 1.0 ClC(Cl)CC(=O)NC2=C(Cl)C(=O)c1ccccc1C2=O

4 <deepchem.feat.mol_graphs.ConvMol object at 0x... -1.952698 1.0 ClC(Cl)C(c1ccc(Cl)cc1)c2ccc(Cl)cc2

... ... ... ... ...

108 <deepchem.feat.mol_graphs.ConvMol object at 0x... 0.646150 1.0 FC(F)(F)C(Cl)Br

109 <deepchem.feat.mol_graphs.ConvMol object at 0x... 1.505805 1.0 CNC(=O)ON=C(SC)C(=O)N(C)C

110 <deepchem.feat.mol_graphs.ConvMol object at 0x... -0.007586 1.0 CCSCCSP(=S)(OC)OC

111 <deepchem.feat.mol_graphs.ConvMol object at 0x... -0.049716 1.0 CCC(C)C

112 <deepchem.feat.mol_graphs.ConvMol object at 0x... -0.684990 1.0 COP(=O)(OC)OC(=CCl)c1cc(Cl)c(Cl)cc1Cl

113 rows × 4 columns

Creating Datasets
Now let's talk about how you can create your own datasets. Creating a NumpyDataset is very simple: just pass the
arrays containing the data to the constructor. Let's create some random arrays, then wrap them in a NumpyDataset.

import numpy as np

X = np.random.random((10, 5))
y = np.random.random((10, 2))
dataset = dc.data.NumpyDataset(X=X, y=y)
print(dataset)

Notice that we did not specify weights or IDs. These are optional, as is y for that matter. Only X is required. Since we
left them out, it automatically built w and ids arrays for us, setting all weights to 1 and setting the IDs to integer
indices.

dataset.to_dataframe()
X1 X2 X3 X4 X5 y1 y2 w ids

0 0.547330 0.919941 0.289138 0.431806 0.776672 0.532579 0.443258 1.0 0

1 0.980867 0.642487 0.460640 0.500153 0.014848 0.678259 0.274029 1.0 1

2 0.953254 0.704446 0.857458 0.378372 0.705789 0.704786 0.901080 1.0 2

3 0.904970 0.729710 0.304247 0.861546 0.917029 0.121747 0.758845 1.0 3

4 0.464144 0.059168 0.600405 0.880529 0.688043 0.595495 0.719861 1.0 4

5 0.820482 0.139002 0.627421 0.129399 0.920024 0.634030 0.464525 1.0 5

6 0.113727 0.551801 0.536189 0.066091 0.311320 0.699331 0.171532 1.0 6

7 0.516131 0.918903 0.429036 0.844973 0.639367 0.464089 0.337989 1.0 7

8 0.809393 0.201450 0.821420 0.841390 0.100026 0.230462 0.376151 1.0 8

9 0.076750 0.389277 0.350371 0.291806 0.127522 0.544606 0.306578 1.0 9

What about creating a DiskDataset? If you have the data in NumPy arrays, you can call DiskDataset.from_numpy() to
save it to disk. Since this is just a tutorial, we will save it to a temporary directory.

import tempfile

with tempfile.TemporaryDirectory() as data_dir:

disk_dataset = dc.data.DiskDataset.from_numpy(X=X, y=y, data_dir=data_dir)
print(disk_dataset)

What about larger datasets that can't fit in memory? What if you have some huge files on disk containing data on
hundreds of millions of molecules? The process for creating a DiskDataset from them is slightly more involved.
Fortunately, DeepChem's DataLoader framework can automate most of the work for you. That is a larger subject, so
we will return to it in a later tutorial.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

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sciences. Join the conversation!
An Introduction To MoleculeNet
By Bharath Ramsundar | Twitter

One of the most powerful features of DeepChem is that it comes "batteries included" with datasets to use. The
DeepChem developer community maintains the MoleculeNet [1] suite of datasets which maintains a large collection of
different scientific datasets for use in machine learning applications. The original MoleculeNet suite had 17 datasets
mostly focused on molecular properties. Over the last several years, MoleculeNet has evolved into a broader collection
of scientific datasets to facilitate the broad use and development of scientific machine learning tools.

These datasets are integrated with the rest of the DeepChem suite so you can conveniently access these through
functions in the dc.molnet submodule. You've already seen a few examples of these loaders already as you've worked
through the tutorial series. The full documentation for the MoleculeNet suite is available in our docs [2].

[1] Wu, Zhenqin, et al. "MoleculeNet: a benchmark for molecular machine learning." Chemical science 9.2 (2018): 513-
530.

[2] https://deepchem.readthedocs.io/en/latest/moleculenet.html

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following installation commands. You can of course run this
tutorial locally if you prefer. In that case, don't run these cells since they will download and install DeepChem again on
your local machine.

!pip install --pre deepchem

We can now import the deepchem package to play with.

import deepchem as dc
dc.__version__

'2.4.0-rc1.dev'

MoleculeNet Overview
In the last two tutorials we loaded the Delaney dataset of molecular solubilities. Let's load it one more time.

tasks, datasets, transformers = dc.molnet.load_delaney(featurizer='GraphConv', splitter='random')

Notice that the loader function we invoke dc.molnet.load_delaney lives in the dc.molnet submodule of
MoleculeNet loaders. Let's take a look at the full collection of loaders available for us

[method for method in dir(dc.molnet) if "load_" in method ]

['load_bace_classification',
'load_bace_regression',
'load_bandgap',
'load_bbbc001',
'load_bbbc002',
'load_bbbp',
'load_cell_counting',
'load_chembl',
'load_chembl25',
'load_clearance',
'load_clintox',
'load_delaney',
'load_factors',
'load_function',
'load_hiv',
'load_hopv',
'load_hppb',
'load_kaggle',
'load_kinase',
'load_lipo',
'load_mp_formation_energy',
'load_mp_metallicity',
'load_muv',
'load_nci',
'load_pcba',
'load_pcba_146',
'load_pcba_2475',
'load_pdbbind',
'load_pdbbind_from_dir',
'load_pdbbind_grid',
'load_perovskite',
'load_ppb',
'load_qm7',
'load_qm7_from_mat',
'load_qm7b_from_mat',
'load_qm8',
'load_qm9',
'load_sampl',
'load_sider',
'load_sweet',
'load_thermosol',
'load_tox21',
'load_toxcast',
'load_uspto',
'load_uv',
'load_zinc15']

The set of MoleculeNet loaders is actively maintained by the DeepChem community and we work on adding new
datasets to the collection. Let's see how many datasets there are in MoleculeNet today

len([method for method in dir(dc.molnet) if "load_" in method ])

MoleculeNet Dataset Categories

There's a lot of different datasets in MoleculeNet. Let's do a quick overview of the different types of datasets available.
We'll break datasets into different categories and list loaders which belong to those categories. More details on each of
these datasets can be found at https://deepchem.readthedocs.io/en/latest/moleculenet.html. The original MoleculeNet
paper [1] provides details about a subset of these papers. We've marked these datasets as "V1" below. All remaining
dataset are "V2" and not documented in the older paper.

Quantum Mechanical Datasets

MoleculeNet's quantum mechanical datasets contain various quantum mechanical property prediction tasks. The current
set of quantum mechanical datasets includes QM7, QM7b, QM8, QM9. The associated loaders are

dc.molnet.load_qm7 : V1
dc.molnet.load_qm7b_from_mat : V1
dc.molnet.load_qm8 : V1
dc.molnet.load_qm9 : V1

Physical Chemistry Datasets

The physical chemistry dataset collection contain a variety of tasks for predicting various physical properties of
molecules.

dc.molnet.load_delaney : V1. This dataset is also referred to as ESOL in the original paper.
dc.molnet.load_sampl : V1. This dataset is also referred to as FreeSolv in the original paper.
dc.molnet.load_lipo : V1. This dataset is also referred to as Lipophilicity in the original paper.
dc.molnet.load_thermosol : V2.
dc.molnet.load_hppb : V2.
dc.molnet.load_hopv : V2. This dataset is drawn from a recent publication [3]

Chemical Reaction Datasets

These datasets hold chemical reaction datasets for use in computational retrosynthesis / forward synthesis.

dc.molnet.load_uspto

Biochemical/Biophysical Datasets
These datasets are drawn from various biochemical/biophysical datasets that measure things like the binding affinity of
compounds to proteins.

dc.molnet.load_pcba : V1
dc.molnet.load_nci : V2.
dc.molnet.load_muv : V1
dc.molnet.load_hiv : V1
dc.molnet.load_ppb : V2.
dc.molnet.load_bace_classification : V1. This loader loads the classification task for the BACE dataset from
the original MoleculeNet paper.
dc.molnet.load_bace_regression : V1. This loader loads the regression task for the BACE dataset from the
original MoleculeNet paper.
dc.molnet.load_kaggle : V2. This dataset is from Merck's drug discovery kaggle contest and is described in [4].
dc.molnet.load_factors : V2. This dataset is from [4].
dc.molnet.load_uv : V2. This dataset is from [4].
dc.molnet.load_kinase : V2. This datset is from [4].

Molecular Catalog Datasets

These datasets provide molecular datasets which have no associated properties beyond the raw SMILES formula or
structure. These types of datasets are useful for generative modeling tasks.

dc.molnet.load_zinc15 : V2
dc.molnet.load_chembl : V2
dc.molnet.load_chembl25 : V2

Physiology Datasets
These datasets measure physiological properties of how molecules interact with human patients.

dc.molnet.load_bbbp : V1
dc.molnet.load_tox21 : V1
dc.molnet.load_toxcast : V1
dc.molnet.load_sider : V1
dc.molnet.load_clintox : V1
dc.molnet.load_clearance : V2.

Structural Biology Datasets

These datasets contain 3D structures of macromolecules along with associated properties.

dc.molnet.load_pdbbind : V1

Microscopy Datasets
These datasets contain microscopy image datasets, typically of cell lines. These datasets were not in the original
MoleculeNet paper.
dc.molnet.load_bbbc001 : V2
dc.molnet.load_bbbc002 : V2
dc.molnet.load_cell_counting : V2

Materials Properties Datasets

These datasets compute properties of various materials.

dc.molnet.load_bandgap : V2
dc.molnet.load_perovskite : V2
dc.molnet.load_mp_formation_energy : V2
dc.molnet.load_mp_metallicity : V2

[3] Lopez, Steven A., et al. "The Harvard organic photovoltaic dataset." Scientific data 3.1 (2016): 1-7.

[4] Ramsundar, Bharath, et al. "Is multitask deep learning practical for pharma?." Journal of chemical information and
modeling 57.8 (2017): 2068-2076.

MoleculeNet Loaders Explained

All MoleculeNet loader functions take the form dc.molnet.load_X . Loader functions return a tuple of arguments
(tasks, datasets, transformers) . Let's walk through each of these return values and explain what we get:

1. tasks : This is a list of task-names. Many datasets in MoleculeNet are "multitask". That is, a given datapoint has
multiple labels associated with it. These correspond to different measurements or values associated with this
datapoint.
2. datasets : This field is a tuple of three dc.data.Dataset objects (train, valid, test) . These correspond to
the training, validation, and test set for this MoleculeNet dataset.
3. transformers : This field is a list of dc.trans.Transformer objects which were applied to this dataset during
processing.

This is abstract so let's take a look at each of these fields for the dc.molnet.load_delaney function we invoked above.
Let's start with tasks .

tasks

['measured log solubility in mols per litre']

We have one task in this dataset which corresponds to the measured log solubility in mol/L. Let's now take a look at
datasets :

datasets

(<DiskDataset X.shape: (902,), y.shape: (902, 1), w.shape: (902, 1), ids: ['CCC(C)Cl' 'O=C1NC(=O)NC(=O)C1(C(C)C
)CC=C' 'Oc1ccccn1' ...
'CCCCCCCC(=O)OCC' 'O=Cc1ccccc1' 'CCCC=C(CC)C=O'], task_names: ['measured log solubility in mols per litre']>,
<DiskDataset X.shape: (113,), y.shape: (113, 1), w.shape: (113, 1), ids: ['CSc1nc(nc(n1)N(C)C)N(C)C' 'CC#N' 'C
CCCCCCC#C' ... 'ClCCBr'
'CCN(CC)C(=O)CSc1ccc(Cl)nn1' 'CC(=O)OC3CCC4C2CCC1=CC(=O)CCC1(C)C2CCC34C '], task_names: ['measured log solubi
lity in mols per litre']>,
<DiskDataset X.shape: (113,), y.shape: (113, 1), w.shape: (113, 1), ids: ['CCCCc1c(C)nc(nc1O)N(C)C '
'Cc3cc2nc1c(=O)[nH]c(=O)nc1n(CC(O)C(O)C(O)CO)c2cc3C'
'CSc1nc(NC(C)C)nc(NC(C)C)n1' ... 'O=c1[nH]cnc2[nH]ncc12 '
'CC(=C)C1CC=C(C)C(=O)C1' 'OC(C(=O)c1ccccc1)c2ccccc2'], task_names: ['measured log solubility in mols per litr
e']>)

As we mentioned previously, we see that datasets is a tuple of 3 datasets. Let's split them out.

train, valid, test = datasets

train

valid

<DiskDataset X.shape: (113,), y.shape: (113, 1), w.shape: (113, 1), ids: ['CSc1nc(nc(n1)N(C)C)N(C)C' 'CC#N' 'CC
CCCCCC#C' ... 'ClCCBr'
'CCN(CC)C(=O)CSc1ccc(Cl)nn1' 'CC(=O)OC3CCC4C2CCC1=CC(=O)CCC1(C)C2CCC34C '], task_names: ['measured log solubil
ity in mols per litre']>
test

Let's peek into one of the datapoints in the train dataset.

train.X[0]

<deepchem.feat.mol_graphs.ConvMol at 0x7fe1ef601438>

Note that this is a dc.feat.mol_graphs.ConvMol object produced by dc.feat.ConvMolFeaturizer . We'll say more
about how to control choice of featurization shortly. Finally let's take a look at the transformers field:

transformers

[<deepchem.trans.transformers.NormalizationTransformer at 0x7fe2029bdfd0>]

So we see that one transformer was applied, the dc.trans.NormalizationTransformer .

After reading through this description so far, you may be wondering what choices are made under the hood. As we've
briefly mentioned previously, datasets can be processed with different choices of "featurizers". Can we control the
choice of featurization here? In addition, how was the source dataset split into train/valid/test as three different
datasets?

You can use the 'featurizer' and 'splitter' keyword arguments and pass in different strings. Common possible choices for
'featurizer' are 'ECFP', 'GraphConv', 'Weave' and 'smiles2img' corresponding to the dc.feat.CircularFingerprint ,
dc.feat.ConvMolFeaturizer , dc.feat.WeaveFeaturizer and dc.feat.SmilesToImage featurizers. Common
possible choices for 'splitter' are None , 'index', 'random', 'scaffold' and 'stratified' corresponding to no split,
dc.splits.IndexSplitter , dc.splits.RandomSplitter , dc.splits.SingletaskStratifiedSplitter . We
haven't talked much about splitters yet, but intuitively they're a way to partition a dataset based on different criteria.
We'll say more in a future tutorial.

Instead of a string, you also can pass in any Featurizer or Splitter object. This is very useful when, for example, a
Featurizer has constructor arguments you can use to customize its behavior.

tasks, datasets, transformers = dc.molnet.load_delaney(featurizer="ECFP", splitter="scaffold")

(train, valid, test) = datasets

train

train.X[0]

array([0., 0., 0., ..., 0., 0., 0.])

Note that unlike the earlier invocation we have numpy arrays produced by dc.feat.CircularFingerprint instead of
ConvMol objects produced by dc.feat.ConvMolFeaturizer .

Give it a try for yourself. Try invoking MoleculeNet to load some other datasets and experiment with different
featurizer/split options and see what happens!

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

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sciences. Join the conversation!
Molecular Fingerprints
Molecules can be represented in many ways. This tutorial introduces a type of representation called a "molecular
fingerprint". It is a very simple representation that often works well for small drug-like molecules.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

We can now import the deepchem package to play with.

import deepchem as dc
dc.__version__

'2.4.0-rc1.dev'

What is a Fingerprint?
Deep learning models almost always take arrays of numbers as their inputs. If we want to process molecules with them,
we somehow need to represent each molecule as one or more arrays of numbers.

Many (but not all) types of models require their inputs to have a fixed size. This can be a challenge for molecules, since
different molecules have different numbers of atoms. If we want to use these types of models, we somehow need to
represent variable sized molecules with fixed sized arrays.

Fingerprints are designed to address these problems. A fingerprint is a fixed length array, where different elements
indicate the presence of different features in the molecule. If two molecules have similar fingerprints, that indicates they
contain many of the same features, and therefore will likely have similar chemistry.

DeepChem supports a particular type of fingerprint called an "Extended Connectivity Fingerprint", or "ECFP" for short.
They also are sometimes called "circular fingerprints". The ECFP algorithm begins by classifying atoms based only on
their direct properties and bonds. Each unique pattern is a feature. For example, "carbon atom bonded to two
hydrogens and two heavy atoms" would be a feature, and a particular element of the fingerprint is set to 1 for any
molecule that contains that feature. It then iteratively identifies new features by looking at larger circular
neighborhoods. One specific feature bonded to two other specific features becomes a higher level feature, and the
corresponding element is set for any molecule that contains it. This continues for a fixed number of iterations, most
often two.

Let's take a look at a dataset that has been featurized with ECFP.

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer='ECFP')

train_dataset, valid_dataset, test_dataset = datasets
print(train_dataset)

The feature array X has shape (6264, 1024). That means there are 6264 samples in the training set. Each one is
represented by a fingerprint of length 1024. Also notice that the label array y has shape (6264, 12): this is a multitask
dataset. Tox21 contains information about the toxicity of molecules. 12 different assays were used to look for signs of
toxicity. The dataset records the results of all 12 assays, each as a different task.

Let's also take a look at the weights array.

train_dataset.w
array([[1.0433141624730409, 1.0369942196531792, 8.53921568627451, ...,
1.060388945752303, 1.1895710249165168, 1.0700990099009902],
[1.0433141624730409, 1.0369942196531792, 1.1326397919375812, ...,
0.0, 1.1895710249165168, 1.0700990099009902],
[0.0, 0.0, 0.0, ..., 1.060388945752303, 0.0, 0.0],
...,
[0.0, 0.0, 0.0, ..., 0.0, 0.0, 0.0],
[1.0433141624730409, 1.0369942196531792, 8.53921568627451, ...,
1.060388945752303, 0.0, 0.0],
[1.0433141624730409, 1.0369942196531792, 1.1326397919375812, ...,
1.060388945752303, 1.1895710249165168, 1.0700990099009902]],
dtype=object)

Notice that some elements are 0. The weights are being used to indicate missing data. Not all assays were actually
performed on every molecule. Setting the weight for a sample or sample/task pair to 0 causes it to be ignored during
fitting and evaluation. It will have no effect on the loss function or other metrics.

Most of the other weights are close to 1, but not exactly 1. This is done to balance the overall weight of positive and
negative samples on each task. When training the model, we want each of the 12 tasks to contribute equally, and on
each task we want to put equal weight on positive and negative samples. Otherwise, the model might just learn that
most of the training samples are non-toxic, and therefore become biased toward identifying other molecules as non-
toxic.

Training a Model on Fingerprints

Let's train a model. In earlier tutorials we use GraphConvModel , which is a fairly complicated architecture that takes a
complex set of inputs. Because fingerprints are so simple, just a single fixed length array, we can use a much simpler
type of model.

model = dc.models.MultitaskClassifier(n_tasks=12, n_features=1024, layer_sizes=[1000])

MultitaskClassifier is a simple stack of fully connected layers. In this example we tell it to use a single hidden layer
of width 1000. We also tell it that each input will have 1024 features, and that it should produce predictions for 12
different tasks.

Why not train a separate model for each task? We could do that, but it turns out that training a single model for multiple
tasks often works better. We will see an example of that in a later tutorial.

Let's train and evaluate the model.

import numpy as np

model.fit(train_dataset, nb_epoch=10)
metric = dc.metrics.Metric(dc.metrics.roc_auc_score)
print('training set score:', model.evaluate(train_dataset, [metric], transformers))
print('test set score:', model.evaluate(test_dataset, [metric], transformers))

training set score: {'roc_auc_score': 0.9550063590563469}

test set score: {'roc_auc_score': 0.7781819573695475}

Not bad performance for such a simple model and featurization. More sophisticated models do slightly better on this
dataset, but not enormously better.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

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sciences. Join the conversation!
Citing This Tutorial
If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro4,
title={Molecular Fingerprints},
organization={DeepChem},
author={Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Molecular_Fingerprints.ipyn
year={2021},
}
Creating Models with TensorFlow and PyTorch
In the tutorials so far, we have used standard models provided by DeepChem. This is fine for many applications, but
sooner or later you will want to create an entirely new model with an architecture you define yourself. DeepChem
provides integration with both TensorFlow (Keras) and PyTorch, so you can use it with models from either of these
frameworks.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

There are actually two different approaches you can take to using TensorFlow or PyTorch models with DeepChem. It
depends on whether you want to use TensorFlow/PyTorch APIs or DeepChem APIs for training and evaluating your
model. For the former case, DeepChem's Dataset class has methods for easily adapting it to use with other
frameworks. make_tf_dataset() returns a tensorflow.data.Dataset object that iterates over the data.
make_pytorch_dataset() returns a torch.utils.data.IterableDataset that iterates over the data. This lets you
use DeepChem's datasets, loaders, featurizers, transformers, splitters, etc. and easily integrate them into your existing
TensorFlow or PyTorch code.

But DeepChem also provides many other useful features. The other approach, which lets you use those features, is to
wrap your model in a DeepChem Model object. Let's look at how to do that.

KerasModel
KerasModel is a subclass of DeepChem's Model class. It acts as a wrapper around a tensorflow.keras.Model . Let's
see an example of using it. For this example, we create a simple sequential model consisting of two dense layers.

import deepchem as dc
import tensorflow as tf

keras_model = tf.keras.Sequential([
tf.keras.layers.Dense(1000, activation='relu'),
tf.keras.layers.Dropout(rate=0.5),
tf.keras.layers.Dense(1)
])
model = dc.models.KerasModel(keras_model, dc.models.losses.L2Loss())

For this example, we used the Keras Sequential class. Our model consists of a dense layer with ReLU activation, 50%
dropout to provide regularization, and a final layer that produces a scalar output. We also need to specify the loss
function to use when training the model, in this case L2 loss. We can now train and evaluate the model exactly as we
would with any other DeepChem model. For example, let's load the Delaney solubility dataset. How does our model do
at predicting the solubilities of molecules based on their extended-connectivity fingerprints (ECFPs)?

tasks, datasets, transformers = dc.molnet.load_delaney(featurizer='ECFP', splitter='random')

train_dataset, valid_dataset, test_dataset = datasets
model.fit(train_dataset, nb_epoch=50)
metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)
print('training set score:', model.evaluate(train_dataset, [metric]))
print('test set score:', model.evaluate(test_dataset, [metric]))

training set score: {'pearson_r2_score': 0.9766804253639305}

test set score: {'pearson_r2_score': 0.7048814451615332}

TorchModel
TorchModel works just like KerasModel , except it wraps a torch.nn.Module . Let's use PyTorch to create another
model just like the previous one and train it on the same data.

import torch

pytorch_model = torch.nn.Sequential(
torch.nn.Linear(1024, 1000),
torch.nn.ReLU(),
torch.nn.Dropout(0.5),
torch.nn.Linear(1000, 1)
)
model = dc.models.TorchModel(pytorch_model, dc.models.losses.L2Loss())

model.fit(train_dataset, nb_epoch=50)
print('training set score:', model.evaluate(train_dataset, [metric]))
print('test set score:', model.evaluate(test_dataset, [metric]))

training set score: {'pearson_r2_score': 0.9760781898204121}

test set score: {'pearson_r2_score': 0.6981331812360332}

Computing Losses
Now let's see a more advanced example. In the above models, the loss was computed directly from the model's output.
Often that is fine, but not always. Consider a classification model that outputs a probability distribution. While it is
possible to compute the loss from the probabilities, it is more numerically stable to compute it from the logits.

To do this, we create a model that returns multiple outputs, both probabilities and logits. KerasModel and
TorchModel let you specify a list of "output types". If a particular output has type 'prediction' , that means it is a
normal output that should be returned when you call predict() . If it has type 'loss' , that means it should be
passed to the loss function in place of the normal outputs.

Sequential models do not allow multiple outputs, so instead we use a subclassing style model.

class ClassificationModel(tf.keras.Model):

def __init__(self):
super(ClassificationModel, self).__init__()
self.dense1 = tf.keras.layers.Dense(1000, activation='relu')
self.dense2 = tf.keras.layers.Dense(1)

def call(self, inputs, training=False):

y = self.dense1(inputs)
if training:
y = tf.nn.dropout(y, 0.5)
logits = self.dense2(y)
output = tf.nn.sigmoid(logits)
return output, logits

keras_model = ClassificationModel()
output_types = ['prediction', 'loss']
model = dc.models.KerasModel(keras_model, dc.models.losses.SigmoidCrossEntropy(), output_types=output_types)

We can train our model on the BACE dataset. This is a binary classification task that tries to predict whether a molecule
will inhibit the enzyme BACE-1.

tasks, datasets, transformers = dc.molnet.load_bace_classification(feturizer='ECFP', splitter='scaffold')

train_dataset, valid_dataset, test_dataset = datasets
model.fit(train_dataset, nb_epoch=100)
metric = dc.metrics.Metric(dc.metrics.roc_auc_score)
print('training set score:', model.evaluate(train_dataset, [metric]))
print('test set score:', model.evaluate(test_dataset, [metric]))

training set score: {'roc_auc_score': 0.9995809177900399}

test set score: {'roc_auc_score': 0.7629528985507246}

Similarly, we will create a custom Classifier Model class to be used with TorchModel . Using similar reasoning to the
above KerasModel , a custom model allows for easy capturing of the unscaled output (logits in Tensorflow) of the
second dense layer. The custom class allows definition of how forward pass is done; enabling capture of the logits right
before the final sigmoid is applied to produce the prediction.

Finally, an instance of ClassificationModel is coupled with a loss function that requires both the prediction and logits
to produce an instance of TorchModel to train.

class ClassificationModel(torch.nn.Module):

def __init__(self):
super(ClassificationModel, self).__init__()
self.dense1 = torch.nn.Linear(1024, 1000)
self.dense2 = torch.nn.Linear(1000, 1)

def forward(self, inputs):

y = torch.nn.functional.relu( self.dense1(inputs) )
y = torch.nn.functional.dropout(y, p=0.5, training=self.training)
logits = self.dense2(y)
output = torch.sigmoid(logits)
return output, logits
torch_model = ClassificationModel()
output_types = ['prediction', 'loss']
model = dc.models.TorchModel(torch_model, dc.models.losses.SigmoidCrossEntropy(), output_types=output_types)

We will use the same BACE dataset. As before, the model will try to do a binary classification task that tries to predict
whether a molecule will inhibit the enzyme BACE-1.

tasks, datasets, transformers = dc.molnet.load_bace_classification(feturizer='ECFP', splitter='scaffold')

training set score: {'roc_auc_score': 0.9996340015366347}

test set score: {'roc_auc_score': 0.7615036231884058}

Other Features
KerasModel and TorchModel have lots of other features. Here are some of the more important ones.

Automatically saving checkpoints during training.

Logging progress to the console, to TensorBoard, or to Weights & Biases.
Custom loss functions that you define with a function of the form f(outputs, labels, weights) .
Early stopping using the ValidationCallback class.
Loading parameters from pre-trained models.
Estimating uncertainty in model outputs.
Identifying important features through saliency mapping.

By wrapping your own models in a KerasModel or TorchModel , you get immediate access to all these features. See
the API documentation for full details on them.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro1,
title={5},
organization={DeepChem},
author={Ramsundar, Bharath and Rebel, Alles},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Creating_Models_with_Tensor
year={2021},
}
Introduction to Graph Convolutions
In this tutorial we will learn more about "graph convolutions." These are one of the most powerful deep learning tools for
working with molecular data. The reason for this is that molecules can be naturally viewed as graphs.

Note how standard chemical diagrams of the sort we're used to from high school lend themselves naturally to
visualizing molecules as graphs. In the remainder of this tutorial, we'll dig into this relationship in significantly more
detail. This will let us get a deeper understanding of how these systems work.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

What are Graph Convolutions?

Consider a standard convolutional neural network (CNN) of the sort commonly used to process images. The input is a
grid of pixels. There is a vector of data values for each pixel, for example the red, green, and blue color channels. The
data passes through a series of convolutional layers. Each layer combines the data from a pixel and its neighbors to
produce a new data vector for the pixel. Early layers detect small scale local patterns, while later layers detect larger,
more abstract patterns. Often the convolutional layers alternate with pooling layers that perform some operation such
as max or min over local regions.

Graph convolutions are similar, but they operate on a graph. They begin with a data vector for each node of the graph
(for example, the chemical properties of the atom that node represents). Convolutional and pooling layers combine
information from connected nodes (for example, atoms that are bonded to each other) to produce a new data vector for
each node.

Training a GraphConvModel
Let's use the MoleculeNet suite to load the Tox21 dataset. To featurize the data in a way that graph convolutional
networks can use, we set the featurizer option to 'GraphConv' . The MoleculeNet call returns a training set, a validation
set, and a test set for us to use. It also returns tasks , a list of the task names, and transformers , a list of data
transformations that were applied to preprocess the dataset. (Most deep networks are quite finicky and require a set of
data transformations to ensure that training proceeds stably.)

Note: While importing deepchem, if you see any warnings, ignore them for now. Deepchem is a vast library and there
are many things that can cause minor warnings to occur. Almost always, it doesn't require any action from your side.
import deepchem as dc

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer='GraphConv')

train_dataset, valid_dataset, test_dataset = datasets

Let's now train a graph convolutional network on this dataset. DeepChem has the class GraphConvModel that wraps a
standard graph convolutional architecture underneath the hood for user convenience. Let's instantiate an object of this
class and train it on our dataset.

n_tasks = len(tasks)
num_features = train_dataset.X[0].get_atom_features().shape[1]
model = dc.models.torch_models.GraphConvModel(n_tasks, mode='classification',number_input_features=[num_features,64
model.fit(train_dataset, nb_epoch=50)

0.29102970123291017

Let's try to evaluate the performance of the model we've trained. For this, we need to define a metric, a measure of
model performance. dc.metrics holds a collection of metrics already. For this dataset, it is standard to use the ROC-
AUC score, the area under the receiver operating characteristic curve (which measures the tradeoff between precision
and recall). Luckily, the ROC-AUC score is already available in DeepChem.

To measure the performance of the model under this metric, we can use the convenience function model.evaluate() .

metric = dc.metrics.Metric(dc.metrics.roc_auc_score)
print('Training set score:', model.evaluate(train_dataset, [metric], transformers))
print('Test set score:', model.evaluate(test_dataset, [metric], transformers))

Training set score: {'roc_auc_score': 0.970785822904073}

Test set score: {'roc_auc_score': 0.7112009940440461}

The results are pretty good, and GraphConvModel is very easy to use. But what's going on under the hood? Could we
build GraphConvModel ourselves? Of course! DeepChem provides Keras layers for all the calculations involved in a
graph convolution. We are going to apply the following layers from DeepChem.

GraphConv layer: This layer implements the graph convolution. The graph convolution combines per-node feature
vectures in a nonlinear fashion with the feature vectors for neighboring nodes. This "blends" information in local
neighborhoods of a graph.

GraphPool layer: This layer does a max-pooling over the feature vectors of atoms in a neighborhood. You can think
of this layer as analogous to a max-pooling layer for 2D convolutions but which operates on graphs instead.

GraphGather : Many graph convolutional networks manipulate feature vectors per graph-node. For a molecule for
example, each node might represent an atom, and the network would manipulate atomic feature vectors that
summarize the local chemistry of the atom. However, at the end of the application, we will likely want to work with a
molecule level feature representation. This layer creates a graph level feature vector by combining all the node-
level feature vectors.

Apart from this we are going to apply standard neural network layers such as Dense, BatchNormalization and Softmax
layer.

Training a custom Graph Convolution network

As you may have seen in the previous tutorials, DeepChem offers both PyTorch and Tensorflow functionalities. However,
most of our work moving forward will leverage the PyTorch ecosystem.

Let's look at the Tensorflow implementation first.

Tensorflow
from deepchem.models.layers import GraphConv, GraphPool, GraphGather
import tensorflow as tf
import tensorflow.keras.layers as layers

batch_size = 100

class GraphConvModelTensorflow(tf.keras.Model):

def __init__(self):
super(GraphConvModelTensorflow, self).__init__()
self.gc1 = GraphConv(128, activation_fn=tf.nn.tanh)
self.batch_norm1 = layers.BatchNormalization()
self.gp1 = GraphPool()
self.gc2 = GraphConv(128, activation_fn=tf.nn.tanh)
self.batch_norm2 = layers.BatchNormalization()
self.gp2 = GraphPool()

self.dense1 = layers.Dense(256, activation=tf.nn.tanh)

self.batch_norm3 = layers.BatchNormalization()
self.readout = GraphGather(batch_size=batch_size, activation_fn=tf.nn.tanh)

self.dense2 = layers.Dense(n_tasks*2)
self.logits = layers.Reshape((n_tasks, 2))
self.softmax = layers.Softmax()

def call(self, inputs):

gc1_output = self.gc1(inputs)
batch_norm1_output = self.batch_norm1(gc1_output)
gp1_output = self.gp1([batch_norm1_output] + inputs[1:])

gc2_output = self.gc2([gp1_output] + inputs[1:])

batch_norm2_output = self.batch_norm1(gc2_output)
gp2_output = self.gp2([batch_norm2_output] + inputs[1:])

dense1_output = self.dense1(gp2_output)
batch_norm3_output = self.batch_norm3(dense1_output)
readout_output = self.readout([batch_norm3_output] + inputs[1:])

logits_output = self.logits(self.dense2(readout_output))
return self.softmax(logits_output)

We can now see more clearly what is happening. There are two convolutional blocks, each consisting of a GraphConv ,
followed by batch normalization, followed by a GraphPool to do max pooling. We finish up with a dense layer, another
batch normalization, a GraphGather to combine the data from all the different nodes, and a final dense layer to
produce the global output.

Let's now create the DeepChem model which will be a wrapper around the Keras model that we just created. We will
also specify the loss function so the model knows the objective to minimize.

model = dc.models.KerasModel(GraphConvModelTensorflow(), loss=dc.models.losses.CategoricalCrossEntropy())

What are the inputs to this model? A graph convolution requires a complete description of each molecule, including the
list of nodes (atoms) and a description of which ones are bonded to each other. In fact, if we inspect the dataset we see
that the feature array contains Python objects of type ConvMol .

test_dataset.X[0]

<deepchem.feat.mol_graphs.ConvMol at 0x7bf66bfa1160>

Models expect arrays of numbers as their inputs, not Python objects. We must convert the ConvMol objects into the
particular set of arrays expected by the GraphConv , GraphPool , and GraphGather layers. Fortunately, the ConvMol
class includes the code to do this, as well as to combine all the molecules in a batch to create a single set of arrays.

The following code creates a Python generator that given a batch of data generates the lists of inputs, labels, and
weights whose values are Numpy arrays. atom_features holds a feature vector of length 75 for each atom. The other
inputs are required to support minibatching in TensorFlow. degree_slice is an indexing convenience that makes it
easy to locate atoms from all molecules with a given degree. membership determines the membership of atoms in
molecules (atom i belongs to molecule membership[i] ). deg_adjs is a list that contains adjacency lists grouped by
atom degree. For more details, check out the code.

from deepchem.metrics import to_one_hot

from deepchem.feat.mol_graphs import ConvMol
import numpy as np

def data_generator(dataset, epochs=1):

for ind, (X_b, y_b, w_b, ids_b) in enumerate(dataset.iterbatches(batch_size, epochs,
deterministic=False, pad_batches=True)):
multiConvMol = ConvMol.agglomerate_mols(X_b)
inputs = [multiConvMol.get_atom_features(), multiConvMol.deg_slice, np.array(multiConvMol.membership)]
for i in range(1, len(multiConvMol.get_deg_adjacency_lists())):
inputs.append(multiConvMol.get_deg_adjacency_lists()[i])
labels = [to_one_hot(y_b.flatten(), 2).reshape(-1, n_tasks, 2)]
weights = [w_b]
yield (inputs, labels, weights)

Now, we can train the model using fit_generator(generator) which will use the generator we've defined to train the
model.

model.fit_generator(data_generator(train_dataset, epochs=50))
0.23354644775390626

Now that we have trained our graph convolutional method, let's evaluate its performance. We again have to use our
defined generator to evaluate model performance.

print('Training set score:', model.evaluate_generator(data_generator(train_dataset), [metric], transformers))

print('Test set score:', model.evaluate_generator(data_generator(test_dataset), [metric], transformers))

Training set score: {'roc_auc_score': 0.8370577643901682}

Test set score: {'roc_auc_score': 0.6610993488016647}

PyTorch
Before working on the PyTorch implementation, we must import a few crucial layers from the torch_models collection.
These are PyTorch implementations of GraphConv , GraphPool and GraphGather which we used in the tensorflow's
implementation as well.

import torch
import torch.nn as nn
from deepchem.models.torch_models.layers import GraphConv, GraphGather, GraphPool

PyTorch's GraphConv requires the number of input features to be specified, hence we can extract that piece of
information by following steps:

1. First we get a sample from the dataset.

2. Next we slice and separate the node_features (which is the first element of the list, hence the index 0).
3. Finally, we obtain the number of features by finding the shape of the array.

sample_batch = next(data_generator(train_dataset))
node_features = sample_batch[0][0]
num_input_features = node_features.shape[1]
print(f"Number of input features: {num_input_features}")

Number of input features: 75

class GraphConvModelTorch(nn.Module):
def __init__(self):
super(GraphConvModelTorch, self).__init__()

self.gc1 = GraphConv(out_channel=128, number_input_features=num_input_features, activation_fn=nn.Tanh())

self.batch_norm1 = nn.BatchNorm1d(128)
self.gp1 = GraphPool()

self.gc2 = GraphConv(out_channel=128, number_input_features=128, activation_fn=nn.Tanh())

self.batch_norm2 = nn.BatchNorm1d(128)
self.gp2 = GraphPool()

self.dense1 = nn.Linear(128, 256)

self.act3 = nn.Tanh()
self.batch_norm3 = nn.BatchNorm1d(256)
self.readout = GraphGather(batch_size=batch_size, activation_fn=nn.Tanh())

self.dense2 = nn.Linear(512, n_tasks * 2)

self.logits = lambda data: data.view(-1, n_tasks, 2)

self.softmax = nn.Softmax(dim=-1)

def forward(self, inputs):

gc1_output = self.gc1(inputs)
batch_norm1_output = self.batch_norm1(gc1_output)
gp1_output = self.gp1([batch_norm1_output] + inputs[1:])

gc2_output = self.gc2([gp1_output] + inputs[1:])

batch_norm2_output = self.batch_norm2(gc2_output)
gp2_output = self.gp2([batch_norm2_output] + inputs[1:])

dense1_output = self.act3(self.dense1(gp2_output))
batch_norm3_output = self.batch_norm3(dense1_output)
readout_output = self.readout([batch_norm3_output] + inputs[1:])

dense2_output = self.dense2(readout_output)
logits_output = self.logits(dense2_output)
softmax_output = self.softmax(logits_output)
return softmax_output

model = dc.models.TorchModel(GraphConvModelTorch(), loss=dc.models.losses.CategoricalCrossEntropy())

model.fit_generator(data_generator(train_dataset, epochs=50))
0.2121513557434082

print('Training set score:', model.evaluate_generator(data_generator(train_dataset), [metric], transformers))

print('Test set score:', model.evaluate_generator(data_generator(test_dataset), [metric], transformers))

Training set score: {'roc_auc_score': 0.9838238607233897}

Test set score: {'roc_auc_score': 0.6923516284964811}

Success! Both the models we've constructed behave nearly identically to GraphConvModel . If you're looking to build
your own custom models, you can follow the examples we've provided here to do so. We hope to see exciting
constructions from your end soon!

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Going Deeper On Molecular Featurizations
One of the most important steps of doing machine learning on molecular data is transforming the data into a form
amenable to the application of learning algorithms. This process is broadly called "featurization" and involves turning a
molecule into a vector or tensor of some sort. There are a number of different ways of doing that, and the choice of
featurization is often dependent on the problem at hand. We have already seen two such methods: molecular
fingerprints, and ConvMol objects for use with graph convolutions. In this tutorial we will look at some of the others.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install -qq --pre deepchem

import deepchem
import warnings
warnings.filterwarnings('ignore')
deepchem.__version__

'2.6.0.dev'

Featurizers
In DeepChem, a method of featurizing a molecule (or any other sort of input) is defined by a Featurizer object. There
are three different ways of using featurizers.

1. When using the MoleculeNet loader functions, you simply pass the name of the featurization method to use. We
have seen examples of this in earlier tutorials, such as featurizer='ECFP' or featurizer='GraphConv' .

2. You also can create a Featurizer and directly apply it to molecules. For example:

import deepchem as dc

featurizer = dc.feat.CircularFingerprint()
print(featurizer(['CC', 'CCC', 'CCO']))

[[0. 0. 0. ... 0. 0. 0.]

[0. 0. 0. ... 0. 0. 0.]
[0. 0. 0. ... 0. 0. 0.]]
[09:05:59] DEPRECATION WARNING: please use MorganGenerator
[09:05:59] DEPRECATION WARNING: please use MorganGenerator
[09:05:59] DEPRECATION WARNING: please use MorganGenerator

3. When creating a new dataset with the DataLoader framework, you can specify a Featurizer to use for processing the
data. We will see this in a future tutorial.

We use propane (CH3CH2CH3, represented by the SMILES string 'CCC' ) as a running example throughout this tutorial.
Many of the featurization methods use conformers of the molecules. A conformer can be generated using the
ConformerGenerator class in deepchem.utils.conformers .

RDKitDescriptors
RDKitDescriptors featurizes a molecule by using RDKit to compute values for a list of descriptors. These are basic
physical and chemical properties: molecular weight, polar surface area, numbers of hydrogen bond donors and
acceptors, etc. This is most useful for predicting things that depend on these high level properties rather than on
detailed molecular structure.

Intrinsic to the featurizer is a set of allowed descriptors, which can be accessed using
RDKitDescriptors.allowedDescriptors . The featurizer uses the descriptors in
rdkit.Chem.Descriptors.descList , checks if they are in the list of allowed descriptors, and computes the descriptor
value for the molecule.

Let's print the values of the first ten descriptors for propane.

from rdkit.Chem.Descriptors import descList

rdkit_featurizer = dc.feat.RDKitDescriptors()
features = rdkit_featurizer(['CCC'])[0]
descriptors = [i[0] for i in descList]
for feature, descriptor in zip(features[:10], descriptors):
print(descriptor, feature)

MaxAbsEStateIndex 2.125
MaxEStateIndex 2.125
MinAbsEStateIndex 1.25
MinEStateIndex 1.25
qed 0.3854706587740357
SPS 6.0
MolWt 44.097
HeavyAtomMolWt 36.033
ExactMolWt 44.062600255999996
NumValenceElectrons 20.0
[09:07:17] DEPRECATION WARNING: please use MorganGenerator
[09:07:17] DEPRECATION WARNING: please use MorganGenerator
[09:07:17] DEPRECATION WARNING: please use MorganGenerator

Of course, there are many more descriptors than this.

print('The number of descriptors present is: ', len(features))

The number of descriptors present is: 210

WeaveFeaturizer and MolGraphConvFeaturizer

We previously looked at graph convolutions, which use ConvMolFeaturizer to convert molecules into ConvMol
objects. Graph convolutions are a special case of a large class of architectures that represent molecules as graphs. They
work in similar ways but vary in the details. For example, they may associate data vectors with the atoms, the bonds
connecting them, or both. They may use a variety of techniques to calculate new data vectors from those in the
previous layer, and a variety of techniques to compute molecule level properties at the end.

DeepChem supports lots of different graph based models. Some of them require molecules to be featurized in slightly
different ways. Because of this, there are two other featurizers called WeaveFeaturizer and
MolGraphConvFeaturizer . They each convert molecules into a different type of Python object that is used by
particular models. When using any graph based model, just check the documentation to see what featurizer you need to
use with it.

CoulombMatrix
All the models we have looked at so far consider only the intrinsic properties of a molecule: the list of atoms that
compose it and the bonds connecting them. When working with flexible molecules, you may also want to consider the
different conformations the molecule can take on. For example, when a drug molecule binds to a protein, the strength of
the binding depends on specific interactions between pairs of atoms. To predict binding strength, you probably want to
consider a variety of possible conformations and use a model that takes them into account when making predictions.

The Coulomb matrix is one popular featurization for molecular conformations. Recall that the electrostatic Coulomb
interaction between two charges is proportional to

where

and

are the charges and

is the distance between them. For a molecule with

atoms, the Coulomb matrix is a

matrix where each element gives the strength of the electrostatic interaction between two atoms. It contains
information both about the charges on the atoms and the distances between them. More information on the functional
forms used can be found here.

To apply this featurizer, we first need a set of conformations for the molecule. We can use the ConformerGenerator
class to do this. It takes a RDKit molecule, generates a set of energy minimized conformers, and prunes the set to only
include ones that are significantly different from each other. Let's try running it for propane.

from rdkit import Chem

generator = dc.utils.ConformerGenerator(max_conformers=5)
propane_mol = generator.generate_conformers(Chem.MolFromSmiles('CCC'))
print("Number of available conformers for propane: ", len(propane_mol.GetConformers()))
Number of available conformers for propane: 1

It only found a single conformer. This shouldn't be surprising, since propane is a very small molecule with hardly any
flexibility. Let's try adding another carbon.

butane_mol = generator.generate_conformers(Chem.MolFromSmiles('CCCC'))
print("Number of available conformers for butane: ", len(butane_mol.GetConformers()))

Number of available conformers for butane: 3

Now we can create a Coulomb matrix for our molecule.

coulomb_mat = dc.feat.CoulombMatrix(max_atoms=20)
features = coulomb_mat(propane_mol)
print(features)
[[[36.8581052 12.48684429 7.5619687 2.85945193 2.85804514
2.85804556 1.4674015 1.46740144 0.91279491 1.14239698
1.14239675 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[12.48684429 36.8581052 12.48684388 1.46551218 1.45850736
1.45850732 2.85689525 2.85689538 1.4655122 1.4585072
1.4585072 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 7.5619687 12.48684388 36.8581052 0.9127949 1.14239695
1.14239692 1.46740146 1.46740145 2.85945178 2.85804504
2.85804493 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 2.85945193 1.46551218 0.9127949 0.5 0.29325367
0.29325369 0.21256978 0.21256978 0.12268391 0.13960187
0.13960185 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 2.85804514 1.45850736 1.14239695 0.29325367 0.5
0.29200271 0.17113413 0.21092513 0.13960186 0.1680002
0.20540029 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 2.85804556 1.45850732 1.14239692 0.29325369 0.29200271
0.5 0.21092513 0.17113413 0.13960187 0.20540032
0.16800016 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 1.4674015 2.85689525 1.46740146 0.21256978 0.17113413
0.21092513 0.5 0.29351308 0.21256981 0.2109251
0.17113412 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 1.46740144 2.85689538 1.46740145 0.21256978 0.21092513
0.17113413 0.29351308 0.5 0.21256977 0.17113412
0.21092513 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0.91279491 1.4655122 2.85945178 0.12268391 0.13960186
0.13960187 0.21256981 0.21256977 0.5 0.29325366
0.29325365 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 1.14239698 1.4585072 2.85804504 0.13960187 0.1680002
0.20540032 0.2109251 0.17113412 0.29325366 0.5
0.29200266 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 1.14239675 1.4585072 2.85804493 0.13960185 0.20540029
0.16800016 0.17113412 0.21092513 0.29325365 0.29200266
0.5 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]
[ 0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0.
0. 0. 0. 0. 0. ]]]

Notice that many elements are 0. To combine multiple molecules in a batch we need all the Coulomb matrices to be the
same size, even if the molecules have different numbers of atoms. We specified max_atoms=20 , so the returned matrix
has size (20, 20). The molecule only has 11 atoms, so only an 11 by 11 submatrix is nonzero.

CoulombMatrixEig
An important feature of Coulomb matrices is that they are invariant to molecular rotation and translation, since the
interatomic distances and atomic numbers do not change. Respecting symmetries like this makes learning easier.
Rotating a molecule does not change its physical properties. If the featurization does change, then the model is forced
to learn that rotations are not important, but if the featurization is invariant then the model gets this property
automatically.

Coulomb matrices are not invariant under another important symmetry: permutations of the atoms' indices. A
molecule's physical properties do not depend on which atom we call "atom 1", but the Coulomb matrix does. To deal
with this, the CoulumbMatrixEig featurizer was introduced, which uses the eigenvalue spectrum of the Coulumb
matrix and is invariant to random permutations of the atom's indices. The disadvantage of this featurization is that it
contains much less information (

eigenvalues instead of an

matrix), so models will be more limited in what they can learn.

CoulombMatrixEig inherits from CoulombMatrix and featurizes a molecule by first computing the Coulomb matrices
for different conformers of the molecule and then computing the eigenvalues for each Coulomb matrix. These
eigenvalues are then padded to account for variation in number of atoms across molecules.

coulomb_mat_eig = dc.feat.CoulombMatrixEig(max_atoms=20)
features = coulomb_mat_eig(propane_mol)
print(features)

[[60.07620303 29.62963149 22.75497781 0.5713786 0.28781332 0.28548338

0.27558187 0.18163794 0.17460999 0.17059719 0.16640098 0.
0. 0. 0. 0. 0. 0.
0. 0. ]]

SMILES Tokenization and Numericalization

So far, we have looked at featurization techniques that translate the implicit structural and physical information in
SMILES data into more explicit features that help our models learn and make predictions. In this section, we will
preprocess SMILES strings into a format that can be fed to sequence models, such as 1D convolutional neural networks
and transformers, and enables these models to learn their own representations of molecular properties.

To prepare SMILES strings for a sequence model, we break them down into lists of substrings (called tokens) and turn
them into lists of integer values (numericalization). Sequence models use those integer values as indices of an
embedding matrix, which contains a vector of floating-point numbers for each token in the vocabulary. These
embedding vectors are updated during model training. This process allows the sequence model to learn its own
representations of the molecular properties implicit in the training data.

We will use DeepChem's BasicSmilesTokenizer and the Tox21 dataset from MoleculeNet to demonstrate the process
of tokenizing SMILES.

import numpy as np

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer="Raw")

train_dataset, valid_dataset, test_dataset = datasets
print(train_dataset)

We loaded the datasets with featurizer="Raw" . Now we obtain the SMILES from their ids attributes.

train_smiles = train_dataset.ids
valid_smiles = valid_dataset.ids
test_smiles = test_dataset.ids
print(train_smiles[:5])

['CC(O)(P(=O)(O)O)P(=O)(O)O' 'CC(C)(C)OOC(C)(C)CCC(C)(C)OOC(C)(C)C'
'OC[C@H](O)[C@@H](O)[C@H](O)CO'
'CCCCCCCC(=O)[O-].CCCCCCCC(=O)[O-].[Zn+2]' 'CC(C)COC(=O)C(C)C']

Next we define our tokenizer and map it onto all our data to convert the SMILES strings into lists of tokens. The
BasicSmilesTokenizer breaks down SMILES roughly at atom level.

tokenizer = dc.feat.smiles_tokenizer.BasicSmilesTokenizer()
train_tok = list(map(tokenizer.tokenize, train_smiles))
valid_tok = list(map(tokenizer.tokenize, valid_smiles))
test_tok = list(map(tokenizer.tokenize, test_smiles))
print(train_tok[0])
len(train_tok)

['C', 'C', '(', 'O', ')', '(', 'P', '(', '=', 'O', ')', '(', 'O', ')', 'O', ')', 'P', '(', '=', 'O', ')', '(', '
O', ')', 'O']
6264

Now we have tokenized versions of all SMILES strings in our dataset. To convert those into lists of integer values we first
need to create a list of all possible tokens in our dataset. That list is called the vocabulary. We also add the empty string
"" to our vocabulary in order to correctly handle trailing zeros when decoding zero-padded numericalized SMILES.

flatten = lambda l: [item for items in l for item in items]

all_toks = flatten(train_tok) + flatten(valid_tok) + flatten(test_tok)

vocab = sorted(set(all_toks + [""]))
print(vocab[:12], "...", vocab[-12:])
len(vocab)

['', '#', '(', ')', '-', '.', '/', '1', '2', '3', '4', '5'] ... ['[n+]', '[n-]', '[nH+]', '[nH]', '[o+]', '[s+]'
, '[se]', '\\', 'c', 'n', 'o', 's']
128

To numericalize tokenized SMILES strings we create a str2int dictionary which assigns a number to each token in the
dictionary. We also create the reverse int2str dictionary and define the corresponding encode and decode
functions. Finally we map the encode function on the tokenized data to obtain numericalized SMILES data.

str2int = {s:i for i, s in enumerate(vocab)}

int2str = {i:s for i, s in enumerate(vocab)}
print(f"str2int: {dict(list(str2int.items())[:5])} ...")
print(f"int2str: {dict(list(int2str.items())[:5])} ...")

str2int: {'': 0, '#': 1, '(': 2, ')': 3, '-': 4} ...

int2str: {0: '', 1: '#', 2: '(', 3: ')', 4: '-'} ...

encode = lambda s: [str2int[tok] for tok in s]

decode = lambda i: [int2str[num] for num in i]
print(train_smiles[0])
print(encode(train_tok[0]))
print("".join(decode(encode(train_tok[0]))))

CC(O)(P(=O)(O)O)P(=O)(O)O
[19, 19, 2, 24, 3, 2, 25, 2, 16, 24, 3, 2, 24, 3, 24, 3, 25, 2, 16, 24, 3, 2, 24, 3, 24]
CC(O)(P(=O)(O)O)P(=O)(O)O

train_num = list(map(encode, train_tok))

valid_num = list(map(encode, valid_tok))
test_num = list(map(encode, test_tok))
print(train_num[0])

[19, 19, 2, 24, 3, 2, 25, 2, 16, 24, 3, 2, 24, 3, 24, 3, 25, 2, 16, 24, 3, 2, 24, 3, 24]

Lastly, we would like to combine all molecules in a dataset in an np.array so they can be served to a model in
batches. To achieve that, all sequences have to be of the same length. As in the CoulombMatrix section, we achieve that
by appending zeros up to a fixed value.

max_len = max(map(len, train_num + valid_num + test_num))

max_len

240

The longest sequence across all Tox21 datasets has length 240 , so we use that as our fixed length. We create a
zero_pad function, map it to all numericalized SMILES, and turn them into np.array s.

zero_pad = lambda x: x + [0] * (max_len - len(x))

train_numpad = np.array(list(map(zero_pad, train_num)))

valid_numpad = np.array(list(map(zero_pad, valid_num)))
test_numpad = np.array(list(map(zero_pad, test_num)))
train_numpad

array([[19, 19, 2, ..., 0, 0, 0],

[19, 19, 2, ..., 0, 0, 0],
[24, 19, 42, ..., 0, 0, 0],
...,
[24, 16, 19, ..., 0, 0, 0],
[19, 19, 2, ..., 0, 0, 0],
[19, 19, 2, ..., 0, 0, 0]])
We can check that the zero-padded data still converts back to the correct SMILES string using the decode function on a
random datapoint.

idx = np.random.randint(0, train_numpad.shape[0], 1).item()

print(train_smiles[idx])
print("".join(decode(train_numpad[idx])))

Cc1cc(C(C)(C)c2ccc(O)c(C)c2)ccc1O
Cc1cc(C(C)(C)c2ccc(O)c(C)c2)ccc1O

The padded data passes the test. It is now in the correct format to be used for training of a sequence model, but it
doesn't yet interface nicely with DeepChem's training framework. To change that, we define a tokenize_smiles
function that combines all the steps spelled out above to process a single datapoint. Additionally, we define a
SmilesFeaturizer that uses our custom tokenize_smiles function in its _featurize method and instanciate it as
smiles_featurizer passing it our vocab and max_len .

def tokenize_smiles(x, vocab, max_len):

tokenizer = dc.feat.smiles_tokenizer.BasicSmilesTokenizer()
str2int = {s:i for i, s in enumerate(vocab)}
encode = lambda s: [str2int[tok] for tok in s]
zero_pad = lambda x: x + [0] * (max_len - len(x))
x = tokenizer.tokenize(x)
x = encode(x)
x = zero_pad(x)
return np.array(x)

class SmilesFeaturizer(dc.feat.Featurizer):
def __init__(self, feat_func, vocab, max_len):
self.feat_func = feat_func
self.vocab = vocab
self.max_len = max_len

def _featurize(self, x):

return self.feat_func(x, self.vocab, self.max_len)

smiles_featurizer = SmilesFeaturizer(tokenize_smiles, vocab, max_len)

Finally, we use the smiles_featurizer to create new Tox21 datasets that contain tokenized and numericalized
SMILES in their X attribute.

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer=smiles_featurizer)

print(datasets[0].X)

[09:24:48] WARNING: not removing hydrogen atom without neighbors

[[19 19 2 ... 0 0 0]
[19 19 2 ... 0 0 0]
[24 19 42 ... 0 0 0]
...
[24 16 19 ... 0 0 0]
[19 19 2 ... 0 0 0]
[19 19 2 ... 0 0 0]]

The datasets are now ready to be used with your custom DeepChem sequence model. Don't forget to wrap your model
into the appropriate DeepChem model class.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro7,
title={Going Deeper on Molecular Featurizations},
organization={DeepChem},
author={Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Going_Deeper_on_Molecular_F
year={2021},
}
Working With Splitters
When using machine learning, you typically divide your data into training, validation, and test sets. The MoleculeNet
loaders do this automatically. But how should you divide up the data? This question seems simple at first, but it turns
out to be quite complicated. There are many ways of splitting up data, and which one you choose can have a big impact
on the reliability of your results. This tutorial introduces some of the splitting methods provided by DeepChem.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

'2.7.1'

Splitters
In DeepChem, a method of splitting samples into multiple datasets is defined by a Splitter object. Choosing an
appropriate method for your data is very important. Otherwise, your trained model may seem to work much better than
it really does.

Consider a typical drug development pipeline. You might begin by screening many thousands of molecules to see if they
bind to your target of interest. Once you find one that seems to work, you try to optimize it by testing thousands of
minor variations on it, looking for one that binds more strongly. Then perhaps you test it in animals and find it has
unacceptable toxicity, so you try more variations to fix the problems.

This has an important consequence for chemical datasets: they often include lots of molecules that are very similar to
each other. If you split the data into training and test sets in a naive way, the training set will include many molecules
that are very similar to the ones in the test set, even if they are not exactly identical. As a result, the model may do very
well on the test set, but then fail badly when you try to use it on other data that is less similar to the training data.

Let's take a look at a few of the splitters found in DeepChem.

• General Splitters
○ RandomSplitter
○ RandomGroupSplitter
○ RandomStratifiedSplitter
○ SingletaskStratifiedSplitter
○ IndexSplitter
○ SpecifiedSplitter
○ TaskSplitter

• Molecular Splitters
○ ScaffoldSplitter
○ MolecularWeightSplitter
○ MaxMinSplitter
○ ButinaSplitter
○ FingerprintSplitter

Let's take a look how different splitters work.

RandomSplitter
This is one of the simplest splitters. It just selects samples for the training, validation, and test sets in a completely
random way.

Didn't we just say that's a bad idea? Well, it depends on your data. If every sample is truly independent of every other,
then this is just as good a way as any to split the data. There is no universally best choice of splitter. It all depends on
your particular dataset, and for some datasets this is a fine choice.
RandomStratifiedSplitter
Some datasets are very unbalanced: only a tiny fraction of all samples are positive. In that case, random splitting may
sometimes lead to the validation or test set having few or even no positive samples for some tasks. That makes it
unable to evaluate performance.

RandomStratifiedSplitter addresses this by dividing up the positive and negative samples evenly. If you ask for a
80/10/10 split, the validation and test sets will contain not just 10% of samples, but also 10% of the positive samples for
each task.

ScaffoldSplitter
This splitter tries to address the problem discussed above where many molecules are very similar to each other. It
identifies the scaffold that forms the core of each molecule, and ensures that all molecules with the same scaffold are
put into the same dataset. This is still not a perfect solution, since two molecules may have different scaffolds but be
very similar in other ways, but it usually is a large improvement over random splitting.

ButinaSplitter
This is another splitter that tries to address the problem of similar molecules. It clusters them based on their molecular
fingerprints, so that ones with similar fingerprints will tend to be in the same dataset. The time required by this splitting
algorithm scales as the square of the number of molecules, so it is mainly useful for small to medium sized datasets.

SpecifiedSplitter
This splitter leaves everything up to the user. You tell it exactly which samples to put in each dataset. This is useful
when you know in advance that a particular splitting is appropriate for your data.

An example is temporal splitting. Consider a research project where you are continually generating and testing new
molecules. As you gain more data, you periodically retrain your model on the steadily growing dataset, then use it to
predict results for other not yet tested molecules. A good way of validating whether this works is to pick a particular
cutoff date, train the model on all data you had at that time, and see how well it predicts other data that was generated
later.

TaskSplitter
Provides a simple interface for splitting datasets task-wise.

For some learning problems, the training and test datasets should have different tasks entirely. This is a different
paradigm from the usual Splitter, which ensures that split datasets have different data points, not different tasks. This
method improves multi-task learning and problem decomposition situations by enhancing their efficiency and
performance.

SingletaskStratifiedSplitter
Another way of splitting data, particularly for classification tasks with imbalanced class distributions is the single-task
stratified splitter. The single-task stratified splitter maintains the class distribution in the original dataset across training,
validation and test sets. This is crucial when working with imbalanced datasets where some classes may be under-
represented.

FingerprintSplitter
Class for doing data splits based on the Tanimoto similarity(Tanimoto similarity measures overlap between two sets
succinctly) between ECFP4 fingerprints(ECFP4 fingerprints encode unique parts of molecules for efficient comparison).

This class tries to split the data such that the molecules in each dataset are as different as possible from the ones in the
other datasets. This makes it a very stringent test of models. Predicting the test and validation sets may require
extrapolating far outside the training data.It splits molecular datasets using Tanimoto similarity scores calculated from
ECFP4 fingerprints. ECFP4, based on Morgan fingerprints, encodes molecular substructures.

MolecularWeightSplitter
Another splitter performs data splits based on molecular weight

Effect of Using Different Splitters

Let's look at an example. We will load the Tox21 toxicity dataset using random, fingerprint, scaffold, and Butina
splitting. For each one we train a model and evaluate it on the training and test sets.
import deepchem as dc

splitters = ['random', 'scaffold', 'butina', 'fingerprint']

metric = dc.metrics.Metric(dc.metrics.roc_auc_score)
for splitter in splitters:
tasks, datasets, transformers = dc.molnet.load_tox21(featurizer='ECFP', splitter=splitter)
train_dataset, valid_dataset, test_dataset = datasets
model = dc.models.MultitaskClassifier(n_tasks=len(tasks), n_features=1024, layer_sizes=[1000])
model.fit(train_dataset, nb_epoch=10)
print('splitter:', splitter)
print('training set score:', model.evaluate(train_dataset, [metric], transformers))
print('test set score:', model.evaluate(test_dataset, [metric], transformers))
print()

splitter: random
training set score: {'roc_auc_score': 0.9554904185889012}
test set score: {'roc_auc_score': 0.7854105497196335}

splitter: scaffold
training set score: {'roc_auc_score': 0.958752269558084}
test set score: {'roc_auc_score': 0.6849149319233084}

splitter: butina
training set score: {'roc_auc_score': 0.9584914471889929}
test set score: {'roc_auc_score': 0.6061155305251504}

splitter: fingerprint
training set score: {'roc_auc_score': 0.954193849465875}
test set score: {'roc_auc_score': 0.6235667313881933}

All of them produce very similar performance on the training set, but the random splitter has much higher performance
on the test set. Scaffold splitting has a lower test set score, and Butina splitting is even lower. Does that mean random
splitting is better? No! It means random splitting doesn't give you an accurate measure of how well your model works.
Because the test set contains lots of molecules that are very similar to ones in the training set, it isn't truly independent.
It makes the model appear to work better than it really does. Scaffold splitting and Butina splitting give a better
indication of what you can expect on independent data in the future.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro8,
title={Working With Splitters},
organization={DeepChem},
author={Eastman, Peter, Mohapatra, Bibhusundar and Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Working_With_Splitters.ipyn
year={2021},
}
Advanced Model Training
In the tutorials so far we have followed a simple procedure for training models: load a dataset, create a model, call
fit() , evaluate it, and call ourselves done. That's fine for an example, but in real machine learning projects the
process is usually more complicated. In this tutorial we will look at a more realistic workflow for training a model.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

Hyperparameter Optimization
Let's start by loading the HIV dataset. It classifies over 40,000 molecules based on whether they inhibit HIV replication.

import deepchem as dc

tasks, datasets, transformers = dc.molnet.load_hiv(featurizer='ECFP', split='scaffold')

train_dataset, valid_dataset, test_dataset = datasets

Now let's train a model on it. We will use a MultitaskClassifier , which is just a stack of dense layers. But that still
leaves a lot of options. How many layers should there be, and how wide should each one be? What dropout rate should
we use? What learning rate?

These are called hyperparameters. The standard way to select them is to try lots of values, train each model on the
training set, and evaluate it on the validation set. This lets us see which ones work best.

You could do that by hand, but usually it's easier to let the computer do it for you. DeepChem provides a selection of
hyperparameter optimization algorithms, which are found in the dc.hyper package. For this example we'll use
GridHyperparamOpt , which is the most basic method. We just give it a list of options for each hyperparameter and it
exhaustively tries all combinations of them.

The lists of options are defined by a dict that we provide. For each of the model's arguments, we provide a list of
values to try. In this example we consider three possible sets of hidden layers: a single layer of width 500, a single layer
of width 1000, or two layers each of width 1000. We also consider two dropout rates (20% and 50%) and two learning
rates (0.001 and 0.0001).

params_dict = {
'n_tasks': [len(tasks)],
'n_features': [1024],
'layer_sizes': [[500], [1000], [1000, 1000]],
'dropouts': [0.2, 0.5],
'learning_rate': [0.001, 0.0001]
}
optimizer = dc.hyper.GridHyperparamOpt(dc.models.MultitaskClassifier)
metric = dc.metrics.Metric(dc.metrics.roc_auc_score)
best_model, best_hyperparams, all_results = optimizer.hyperparam_search(
params_dict, train_dataset, valid_dataset, metric, transformers)

hyperparam_search() returns three arguments: the best model it found, the hyperparameters for that model, and a
full listing of the validation score for every model. Let's take a look at the last one.

all_results
{'_dropouts_0.200000_layer_sizes[500]_learning_rate_0.001000_n_features_1024_n_tasks_1': 0.759624393738977,
'_dropouts_0.200000_layer_sizes[500]_learning_rate_0.000100_n_features_1024_n_tasks_1': 0.7680791323731138,
'_dropouts_0.500000_layer_sizes[500]_learning_rate_0.001000_n_features_1024_n_tasks_1': 0.7623870149911817,
'_dropouts_0.500000_layer_sizes[500]_learning_rate_0.000100_n_features_1024_n_tasks_1': 0.7552282358416618,
'_dropouts_0.200000_layer_sizes[1000]_learning_rate_0.001000_n_features_1024_n_tasks_1': 0.7689915858318636,
'_dropouts_0.200000_layer_sizes[1000]_learning_rate_0.000100_n_features_1024_n_tasks_1': 0.7619292572996277,
'_dropouts_0.500000_layer_sizes[1000]_learning_rate_0.001000_n_features_1024_n_tasks_1': 0.7641491524593376,
'_dropouts_0.500000_layer_sizes[1000]_learning_rate_0.000100_n_features_1024_n_tasks_1': 0.7609877155594749,
'_dropouts_0.200000_layer_sizes[1000, 1000]_learning_rate_0.001000_n_features_1024_n_tasks_1': 0.7707169802077
21,
'_dropouts_0.200000_layer_sizes[1000, 1000]_learning_rate_0.000100_n_features_1024_n_tasks_1': 0.7750327625906
329,
'_dropouts_0.500000_layer_sizes[1000, 1000]_learning_rate_0.001000_n_features_1024_n_tasks_1': 0.7259723140799
53,
'_dropouts_0.500000_layer_sizes[1000, 1000]_learning_rate_0.000100_n_features_1024_n_tasks_1': 0.7546280986674
505}

We can see a few general patterns. Using two layers with the larger learning rate doesn't work very well. It seems the
deeper model requires a smaller learning rate. We also see that 20% dropout usually works better than 50%. Once we
narrow down the list of models based on these observations, all the validation scores are very close to each other,
probably close enough that the remaining variation is mainly noise. It doesn't seem to make much difference which of
the remaining hyperparameter sets we use, so let's arbitrarily pick a single layer of width 1000 and learning rate of
0.0001.

Early Stopping
There is one other important hyperparameter we haven't considered yet: how long we train the model for.
GridHyperparamOpt trains each for a fixed, fairly small number of epochs. That isn't necessarily the best number.

You might expect that the longer you train, the better your model will get, but that isn't usually true. If you train too
long, the model will usually start overfitting to irrelevant details of the training set. You can tell when this happens
because the validation set score stops increasing and may even decrease, while the score on the training set continues
to improve.

Fortunately, we don't need to train lots of different models for different numbers of steps to identify the optimal number.
We just train it once, monitor the validation score, and keep whichever parameters maximize it. This is called "early
stopping". DeepChem's ValidationCallback class can do this for us automatically. In the example below, we have it
compute the validation set's ROC AUC every 1000 training steps. If you add the save_dir argument, it will also save a
copy of the best model parameters to disk.

model = dc.models.MultitaskClassifier(n_tasks=len(tasks),
n_features=1024,
layer_sizes=[1000],
dropouts=0.2,
learning_rate=0.0001)
callback = dc.models.ValidationCallback(valid_dataset, 1000, metric)
model.fit(train_dataset, nb_epoch=50, callbacks=callback)

Step 1000 validation: roc_auc_score=0.759757

Step 2000 validation: roc_auc_score=0.770685
Step 3000 validation: roc_auc_score=0.771588
Step 4000 validation: roc_auc_score=0.777862
Step 5000 validation: roc_auc_score=0.773894
Step 6000 validation: roc_auc_score=0.763762
Step 7000 validation: roc_auc_score=0.766361
Step 8000 validation: roc_auc_score=0.767026
Step 9000 validation: roc_auc_score=0.761239
Step 10000 validation: roc_auc_score=0.761279
Step 11000 validation: roc_auc_score=0.765363
Step 12000 validation: roc_auc_score=0.769481
Step 13000 validation: roc_auc_score=0.768523
Step 14000 validation: roc_auc_score=0.761306
Step 15000 validation: roc_auc_score=0.77397
Step 16000 validation: roc_auc_score=0.764848
0.8040038299560547

Learning Rate Schedules

In the examples above we use a fixed learning rate throughout training. In some cases it works better to vary the
learning rate during training. To do this in DeepChem, we simply specify a LearningRateSchedule object instead of a
number for the learning_rate argument. In the following example we use a learning rate that decreases
exponentially. It starts at 0.0002, then gets multiplied by 0.9 after every 1000 steps.

learning_rate = dc.models.optimizers.ExponentialDecay(0.0002, 0.9, 1000)

model = dc.models.MultitaskClassifier(n_tasks=len(tasks),
n_features=1024,
layer_sizes=[1000],
dropouts=0.2,
learning_rate=learning_rate)
model.fit(train_dataset, nb_epoch=50, callbacks=callback)

Step 1000 validation: roc_auc_score=0.736547

Step 2000 validation: roc_auc_score=0.758979
Step 3000 validation: roc_auc_score=0.768361
Step 4000 validation: roc_auc_score=0.764898
Step 5000 validation: roc_auc_score=0.775253
Step 6000 validation: roc_auc_score=0.779898
Step 7000 validation: roc_auc_score=0.76991
Step 8000 validation: roc_auc_score=0.771515
Step 9000 validation: roc_auc_score=0.773796
Step 10000 validation: roc_auc_score=0.776977
Step 11000 validation: roc_auc_score=0.778866
Step 12000 validation: roc_auc_score=0.777066
Step 13000 validation: roc_auc_score=0.77616
Step 14000 validation: roc_auc_score=0.775646
Step 15000 validation: roc_auc_score=0.772785
Step 16000 validation: roc_auc_score=0.769975
0.22854619979858398

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Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro9,
title={Advanced Model Training},
organization={DeepChem},
author={Eastman, Peter and Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Advanced_Model_Training.ipy
year={2021},
}
Creating a High Fidelity Dataset from Experimental Data
In this tutorial, we will look at what is involved in creating a new Dataset from experimental data. As we will see, the
mechanics of creating the Dataset object is only a small part of the process. Most real datasets need significant cleanup
and QA before they are suitable for training models.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

Working With Data Files

Suppose you were given data collected by an experimental collaborator. You would like to use this data to construct a
machine learning model.

How do you transform this data into a dataset capable of creating a useful model?

Building models from novel data can present several challenges. Perhaps the data was not recorded in a convenient
manner. Additionally, perhaps the data contains noise. This is a common occurrence with, for example, biological assays
due to the large number of external variables and the difficulty and cost associated with collecting multiple samples.
This is a problem because you do not want your model to fit to this noise.

Hence, there are two primary challenges:

Parsing data
De-noising data

In this tutorial, we will walk through an example of curating a dataset from an excel spreadsheet of experimental drug
measurements. Before we dive into this example though, let's do a brief review of DeepChem's input file handling and
featurization capabilities.

Input Formats
DeepChem supports a whole range of input files. For example, accepted input formats include .csv, .sdf, .fasta, .png, .tif
and other file formats. The loading for a particular file format is governed by the Loader class associated with that
format. For example, to load a .csv file we use the CSVLoader class. Here's an example of a .csv file that fits the
requirements of CSVLoader .

1. A column containing SMILES strings.

2. A column containing an experimental measurement.
3. (Optional) A column containing a unique compound identifier.

Here's an example of a potential input file.

Compound ID measured log solubility in mols per litre smiles

benzothiazole -1.5 c2ccc1scnc1c2

Here the "smiles" column contains the SMILES string, the "measured log solubility in mols per litre" contains the
experimental measurement, and "Compound ID" contains the unique compound identifier.

Data Featurization
Most machine learning algorithms require that input data form vectors. However, input data for drug-discovery datasets
routinely come in the form of lists of molecules and associated experimental readouts. To load the data, we use a
subclass of dc.data.DataLoader such as dc.data.CSVLoader or dc.data.SDFLoader . Users can subclass
dc.data.DataLoader to load arbitrary file formats. All loaders must be passed a dc.feat.Featurizer object, which
specifies how to transform molecules into vectors. DeepChem provides a number of different subclasses of
dc.feat.Featurizer .
Parsing data
In order to read in the data, we will use the pandas data analysis library.

In order to convert the drug names into smiles strings, we will use pubchempy. This isn't a standard DeepChem
dependency, but you can install this library with conda install pubchempy .

!conda install pubchempy

import os
import pandas as pd
from pubchempy import get_cids, get_compounds

Pandas is magic but it doesn't automatically know where to find your data of interest. You likely will have to look at it
first using a GUI.

We will now look at a screenshot of this dataset as rendered by LibreOffice.

To do this, we will import Image and os.

import os
from IPython.display import Image, display
current_dir = os.path.dirname(os.path.realpath('__file__'))
data_screenshot = os.path.join(current_dir, 'assets/dataset_preparation_gui.png')
display(Image(filename=data_screenshot))

We see the data of interest is on the second sheet, and contained in columns "TA ID", "N #1 (%)", and "N #2 (%)".

Additionally, it appears much of this spreadsheet was formatted for human readability (multicolumn headers, column
labels with spaces and symbols, etc.). This makes the creation of a neat dataframe object harder. For this reason we will
cut everything that is unnecesary or inconvenient.

import deepchem as dc
dc.utils.download_url(
'https://github.com/deepchem/deepchem/raw/master/datasets/Positive%20Modulators%20Summary_%20918.TUC%20_%20v1.xls
current_dir,
'Positive Modulators Summary_ 918.TUC _ v1.xlsx'
)

raw_data_file = os.path.join(current_dir, 'Positive Modulators Summary_ 918.TUC _ v1.xlsx')

raw_data_excel = pd.ExcelFile(raw_data_file)

# second sheet only

raw_data = raw_data_excel.parse(raw_data_excel.sheet_names[1])

# preview 5 rows of raw dataframe

raw_data.loc[raw_data.index[:5]]
Unnamed: Unnamed: Metric #1 (-120 Unnamed: Unnamed: Unnamed:
Unnamed: 2 Unnamed: 5
0 1 mV Peak) 4 6 7

0 NaN NaN NaN Vehicle NaN 4 Replications NaN

Threshold (%) =
1 TA ## Position TA ID Mean SD N #1 (%) N #2 (%)
Mean + 4xSD

Penicillin V
2 1 1-A02 -12.8689 6.74705 14.1193 -10.404 -18.1929
Potassium

Mycophenolate
3 2 1-A03 -12.8689 6.74705 14.1193 -12.4453 -11.7175
Mofetil

4 3 1-A04 Metaxalone -12.8689 6.74705 14.1193 -8.65572 -17.7753

Note that the actual row headers are stored in row 1 and not 0 above.

# remove column labels (rows 0 and 1), as we will replace them

# only take data given in columns "TA ID" "N #1 (%)" (3) and "N #2 (%)" (4)
raw_data = raw_data.iloc[2:, [2, 6, 7]]

# reset the index so we keep the label but number from 0 again
raw_data.reset_index(inplace=True)

## rename columns
raw_data.columns = ['label', 'drug', 'n1', 'n2']

# preview cleaner dataframe

raw_data.loc[raw_data.index[:5]]

label drug n1 n2

0 2 Penicillin V Potassium -10.404 -18.1929

1 3 Mycophenolate Mofetil -12.4453 -11.7175

2 4 Metaxalone -8.65572 -17.7753

3 5 Terazosin·HCl -11.5048 16.0825

4 6 Fluvastatin·Na -11.1354 -14.553

This formatting is closer to what we need.

Now, let's take the drug names and get smiles strings for them (format needed for DeepChem).

drugs = raw_data['drug'].values

For many of these, we can retreive the smiles string via the canonical_smiles attribute of the get_compounds object
(using pubchempy )

get_compounds(drugs[1], 'name')

[Compound(5281078)]

get_compounds(drugs[1], 'name')[0].canonical_smiles

'CC1=C2COC(=O)C2=C(C(=C1OC)CC=C(C)CCC(=O)OCCN3CCOCC3)O'

However, some of these drug names have variables spaces and symbols (·, (±), etc.), and names that may not be
readable by pubchempy.

For this task, we will do a bit of hacking via regular expressions. Also, we notice that all ions are written in a shortened
form that will need to be expanded. For this reason we use a dictionary, mapping the shortened ion names to versions
recognizable to pubchempy.

Unfortunately you may have several corner cases that will require more hacking.

import re

ion_replacements = {
'HBr': ' hydrobromide',
'2Br': ' dibromide',
'Br': ' bromide',
'HCl': ' hydrochloride',
'2H2O': ' dihydrate',
'H20': ' hydrate',
'Na': ' sodium'
}

ion_keys = ['H20', 'HBr', 'HCl', '2Br', '2H2O', 'Br', 'Na']

def compound_to_smiles(cmpd):
# remove spaces and irregular characters
compound = re.sub(r'([^\s\w]|_)+', '', cmpd)

# replace ion names if needed

for ion in ion_keys:
if ion in compound:
compound = compound.replace(ion, ion_replacements[ion])

# query for cid first in order to avoid timeouterror

cid = get_cids(compound, 'name')[0]
smiles = get_compounds(cid)[0].canonical_smiles

return smiles

Now let's actually convert all these compounds to smiles. This conversion will take a few minutes so might not be a bad
spot to go grab a coffee or tea and take a break while this is running! Note that this conversion will sometimes fail so
we've added some error handling to catch these cases below.

smiles_map = {}
for i, compound in enumerate(drugs):
try:
smiles_map[compound] = compound_to_smiles(compound)
except:
print("Errored on %s" % i)
continue

Errored on 162
Errored on 303

smiles_data = raw_data
# map drug name to smiles string
smiles_data['drug'] = smiles_data['drug'].apply(lambda x: smiles_map[x] if x in smiles_map else None)

# preview smiles data

smiles_data.loc[smiles_data.index[:5]]

label drug n1 n2

0 2 CC1(C(N2C(S1)C(C2=O)NC(=O)COC3=CC=CC=C3)C(=O)[... -10.404 -18.1929

1 3 CC1=C2COC(=O)C2=C(C(=C1OC)CC=C(C)CCC(=O)OCCN3C... -12.4453 -11.7175

2 4 CC1=CC(=CC(=C1)OCC2CNC(=O)O2)C -8.65572 -17.7753

3 5 COC1=C(C=C2C(=C1)C(=NC(=N2)N3CCN(CC3)C(=O)C4CC... -11.5048 16.0825

4 6 CC(C)N1C2=CC=CC=C2C(=C1C=CC(CC(CC(=O)[O-])O)O)... -11.1354 -14.553

Hooray, we have mapped each drug name to its corresponding smiles code.

Now, we need to look at the data and remove as much noise as possible.

De-noising data
In machine learning, we know that there is no free lunch. You will need to spend time analyzing and understanding your
data in order to frame your problem and determine the appropriate model framework. Treatment of your data will
depend on the conclusions you gather from this process.

Questions to ask yourself:

What are you trying to accomplish?

What is your assay?
What is the structure of the data?
Does the data make sense?
What has been tried previously?

For this project (respectively):

I would like to build a model capable of predicting the affinity of an arbitrary small molecule drug to a particular ion
channel protein
For an input drug, data describing channel inhibition
A few hundred drugs, with n=2
Will need to look more closely at the dataset*
Nothing on this particular protein

*This will involve plotting, so we will import matplotlib and seaborn. We will also need to look at molecular structures, so
we will import rdkit. We will also use the seaborn library which you can install with conda install seaborn .

import matplotlib.pyplot as plt

%matplotlib inline

import seaborn as sns

sns.set_style('white')

from rdkit import Chem

from rdkit.Chem import AllChem
from rdkit.Chem import Draw, PyMol, rdFMCS
from rdkit.Chem.Draw import IPythonConsole
from rdkit import rdBase
import numpy as np

Our goal is to build a small molecule model, so let's make sure our molecules are all small. This can be approximated by
the length of each smiles string.

smiles_data['len'] = [len(i) if i is not None else 0 for i in smiles_data['drug']]

smiles_lens = [len(i) if i is not None else 0 for i in smiles_data['drug']]
sns.histplot(smiles_lens)
plt.xlabel('len(smiles)')
plt.ylabel('probability')

Text(0, 0.5, 'probability')

Some of these look rather large, len(smiles) > 150. Let's see what they look like.

# indices of large looking molecules

suspiciously_large = np.where(np.array(smiles_lens) > 150)[0]

# corresponding smiles string

long_smiles = smiles_data.loc[smiles_data.index[suspiciously_large]]['drug'].values

# look
Draw._MolsToGridImage([Chem.MolFromSmiles(i) for i in long_smiles], molsPerRow=6)

As suspected, these are not small molecules, so we will remove them from the dataset. The argument here is that these
molecules could register as inhibitors simply because they are large. They are more likely to sterically block the
channel, rather than diffuse inside and bind (which is what we are interested in).

The lesson here is to remove data that does not fit your use case.

# drop large molecules

smiles_data = smiles_data[~smiles_data['drug'].isin(long_smiles)]

Now, let's look at the numerical structure of the dataset.

First, check for NaNs.

nan_rows = smiles_data[smiles_data.isnull().T.any().T]
nan_rows[['n1', 'n2']]

n1 n2

62 NaN -7.8266

162 -12.8456 -11.4627

175 NaN -6.61225

187 NaN -8.23326

233 -8.21781 NaN

262 NaN -12.8788

288 NaN -2.34264

300 NaN -8.19936

301 NaN -10.4633

303 -5.61374 8.42267

311 NaN -8.78722

I don't trust n=1, so I will throw these out.

Then, let's examine the distribution of n1 and n2.

df = smiles_data.dropna(axis=0, how='any')
# seaborn jointplot will allow us to compare n1 and n2, and plot each marginal
sns.jointplot(x='n1', y='n2', data=smiles_data)

<seaborn.axisgrid.JointGrid at 0x14c4e37d0>

We see that most of the data is contained in the gaussian-ish blob centered a bit below zero. We see that there are a
few clearly active datapoints located in the bottom left, and one on the top right. These are all distinguished from the
majority of the data. How do we handle the data in the blob?

Because n1 and n2 represent the same measurement, ideally they would be of the same value. This plot should be
tightly aligned to the diagonal, and the pearson correlation coefficient should be 1. We see this is not the case. This
helps gives us an idea of the error of our assay.

Let's look at the error more closely, plotting in the distribution of (n1-n2).

diff_df = df['n1'] - df['n2']

sns.histplot(diff_df)
plt.xlabel('difference in n')
plt.ylabel('probability')

Text(0, 0.5, 'probability')

This looks pretty gaussian, let's get the 95% confidence interval by fitting a gaussian via scipy, and taking 2*the
standard deviation

from scipy import stats

mean, std = stats.norm.fit(np.asarray(diff_df, dtype=np.float32))
ci_95 = std*2
ci_95

17.75387954711914

Now, I don't trust the data outside of the confidence interval, and will therefore drop these datapoints from df.

For example, in the plot above, at least one datapoint has n1-n2 > 60. This is disconcerting.

noisy = diff_df[abs(diff_df) > ci_95]

df = df.drop(noisy.index)
sns.jointplot(x='n1', y='n2', data=df)

<seaborn.axisgrid.JointGrid at 0x15a363c10>

Now that data looks much better!

So, let's average n1 and n2, and take the error bar to be ci_95.

avg_df = df[['label', 'drug']].copy()

n_avg = df[['n1', 'n2']].mean(axis=1)
avg_df['n'] = n_avg
avg_df.sort_values('n', inplace=True)

Now, let's look at the sorted data with error bars.

plt.errorbar(np.arange(avg_df.shape[0]), avg_df['n'], yerr=ci_95, fmt='o')

plt.xlabel('drug, sorted')
plt.ylabel('activity')

Text(0, 0.5, 'activity')

Now, let's identify our active compounds.

In my case, this required domain knowledge. Having worked in this area, and having consulted with professors
specializing on this channel, I am interested in compounds where the absolute value of the activity is greater than 25.
This relates to the desired drug potency we would like to model.

If you are not certain how to draw the line between active and inactive, this cutoff could potentially be treated as a
hyperparameter.

actives = avg_df[abs(avg_df['n'])-ci_95 > 25]['n']

plt.errorbar(np.arange(actives.shape[0]), actives, yerr=ci_95, fmt='o')

<ErrorbarContainer object of 3 artists>

# summary
print (raw_data.shape, avg_df.shape, len(actives.index))

(430, 5) (392, 3) 6

In summary, we have:

Removed data that did not address the question we hope to answer (small molecules only)
Dropped NaNs
Determined the noise of our measurements
Removed exceptionally noisy datapoints
Identified actives (using domain knowledge to determine a threshold)

Determine model type, final form of dataset, and sanity load

Now, what model framework should we use?

Given that we have 392 datapoints and 6 actives, this data will be used to build a low data one-shot classifier
(10.1021/acscentsci.6b00367). If there were datasets of similar character, transfer learning could potentially be used,
but this is not the case at the moment.

Let's apply logic to our dataframe in order to cast it into a binary format, suitable for classification.

# 1 if condition for active is met, 0 otherwise

avg_df.loc[:, 'active'] = (abs(avg_df['n'])-ci_95 > 25).astype(int)

Now, save this to file.

avg_df.to_csv('modulators.csv', index=False)

Now, we will convert this dataframe to a DeepChem dataset.

dataset_file = 'modulators.csv'
task = ['active']
featurizer_func = dc.feat.ConvMolFeaturizer()

loader = dc.data.CSVLoader(tasks=task, feature_field='drug', featurizer=featurizer_func)

dataset = loader.create_dataset(dataset_file)

Lastly, it is often advantageous to numerically transform the data in some way. For example, sometimes it is useful to
normalize the data, or to zero the mean. This depends in the task at hand.

Built into DeepChem are many useful transformers, located in the deepchem.transformers.transformers base class.

Because this is a classification model, and the number of actives is low, I will apply a balancing transformer. I treated
this transformer as a hyperparameter when I began training models. It proved to unambiguously improve model
performance.

transformer = dc.trans.BalancingTransformer(dataset=dataset)
dataset = transformer.transform(dataset)

Now let's save the balanced dataset object to disk, and then reload it as a sanity check.

dc.utils.save_to_disk(dataset, 'balanced_dataset.joblib')
balanced_dataset = dc.utils.load_from_disk('balanced_dataset.joblib')

Tutorial written by Keri McKiernan (github.com/kmckiern) on September 8, 2016

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Bibliography
[2] Anderson, Eric, Gilman D. Veith, and David Weininger. "SMILES, a line notation and computerized interpreter for
chemical structures." US Environmental Protection Agency, Environmental Research Laboratory, 1987.

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro10,
title={Creating a high fidelity model from experimental data},
organization={DeepChem},
author={Eastman, Peter and Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/tree/master/examples/tutorials}},
year={2021},
}
Putting Multitask Learning to Work
This notebook walks through the creation of multitask models on MUV [1]. The goal is to demonstrate how multitask
methods can provide improved performance in situations with little or very unbalanced data.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

The MUV dataset is a challenging benchmark in molecular design that consists of 17 different "targets" where there are
only a few "active" compounds per target. There are 93,087 compounds in total, yet no task has more than 30 active
compounds, and many have even less. Training a model with such a small number of positive examples is very
challenging. Multitask models address this by training a single model that predicts all the different targets at once. If a
feature is useful for predicting one task, it often is useful for predicting several other tasks as well. Each added task
makes it easier to learn important features, which improves performance on other tasks [2].

To get started, let's load the MUV dataset. The MoleculeNet loader function automatically splits it into training,
validation, and test sets. Because there are so few positive examples, we use stratified splitting to ensure the test set
has enough of them to evaluate.

import deepchem as dc
import numpy as np

tasks, datasets, transformers = dc.molnet.load_muv(split='stratified')

train_dataset, valid_dataset, test_dataset = datasets

Now let's train a model on it. We'll use a MultitaskClassifier, which is a simple stack of fully connected layers.

n_tasks = len(tasks)
n_features = train_dataset.get_data_shape()[0]
model = dc.models.MultitaskClassifier(n_tasks, n_features)
model.fit(train_dataset)

0.0004961589723825455

Let's see how well it does on the test set. We loop over the 17 tasks and compute the ROC AUC for each one.

y_true = test_dataset.y
y_pred = model.predict(test_dataset)
metric = dc.metrics.roc_auc_score
for i in range(n_tasks):
score = metric(dc.metrics.to_one_hot(y_true[:,i]), y_pred[:,i])
print(tasks[i], score)

MUV-466 0.9207684040838259
MUV-548 0.7480655561526062
MUV-600 0.9927995701235895
MUV-644 0.9974207415368082
MUV-652 0.7823481998925309
MUV-689 0.6636843990686011
MUV-692 0.6319093677234462
MUV-712 0.7787838079885365
MUV-713 0.7910711087229088
MUV-733 0.4401307540748701
MUV-737 0.34679383843811573
MUV-810 0.9564571019165323
MUV-832 0.9991044241447251
MUV-846 0.7519881783987103
MUV-852 0.8516747268493642
MUV-858 0.5906591438294824
MUV-859 0.5962954008166774

Not bad! Recall that random guessing would produce a ROC AUC score of 0.5, and a perfect predictor would score 1.0.
Most of the tasks did much better than random guessing, and many of them are above 0.9.
Congratulations! Time to join the Community!
Congratulations on completing this tutorial notebook! If you enjoyed working through the tutorial, and want to continue
working with DeepChem, we encourage you to finish the rest of the tutorials in this series. You can also help the
DeepChem community in the following ways:

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Bibliography
[1] https://pubs.acs.org/doi/10.1021/ci8002649

[2] https://pubs.acs.org/doi/abs/10.1021/acs.jcim.7b00146
Tutorial Part 13: Modeling Protein-Ligand Interactions
By Nathan C. Frey | Twitter and Bharath Ramsundar | Twitter

In this tutorial, we'll walk you through the use of machine learning and molecular docking methods to predict the
binding energy of a protein-ligand complex. Recall that a ligand is some small molecule which interacts (usually non-
covalently) with a protein. Molecular docking performs geometric calculations to find a “binding pose” with a small
molecule interacting with a protein in a suitable binding pocket (that is, a region on the protein which has a groove in
which the small molecule can rest).

The structure of proteins can be determined experimentally with techniques like Cryo-EM or X-ray crystallography. This
can be a powerful tool for structure-based drug discovery. For more info on docking, read the AutoDock Vina paper and
the deepchem.dock documentation. There are many graphical user and command line interfaces (like AutoDock) for
performing molecular docking. Here, we show how docking can be performed programmatically with DeepChem, which
enables automation and easy integration with machine learning pipelines.

As you work through the tutorial, you'll trace an arc including

1. Loading a protein-ligand complex dataset (PDBbind)

2. Performing programmatic molecular docking
3. Featurizing protein-ligand complexes with interaction fingerprints
4. Fitting a random forest model and predicting binding affinities

To start the tutorial, we'll use a simple pre-processed dataset file that comes in the form of a gzipped file. Each row is a
molecular system, and each column represents a different piece of information about that system. For instance, in this
example, every row reflects a protein-ligand complex, and the following columns are present: a unique complex
identifier; the SMILES string of the ligand; the binding affinity (Ki) of the ligand to the protein in the complex; a Python
list of all lines in a PDB file for the protein alone; and a Python list of all lines in a ligand file for the ligand alone.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!pip install -q condacolab

import condacolab
condacolab.install()

WARNING: Running pip as the 'root' user can result in broken permissions and conflicting behaviour with the syst
em package manager. It is recommended to use a virtual environment instead: https://pip.pypa.io/warnings/venv
✨ ✨ Everything looks OK!

!conda install -c conda-forge openmm

Collecting package metadata (current_repodata.json): - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \

| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / done
Solving environment: \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / done

# All requested packages already installed.

!pip install deepchem

Looking in indexes: https://pypi.org/simple, https://us-python.pkg.dev/colab-wheels/public/simple/
Requirement already satisfied: deepchem in /usr/local/lib/python3.10/site-packages (2.7.1)
Requirement already satisfied: numpy>=1.21 in /usr/local/lib/python3.10/site-packages (from deepchem) (1.24.3)
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Requirement already satisfied: pandas in /usr/local/lib/python3.10/site-packages (from deepchem) (2.0.1)
Requirement already satisfied: rdkit in /usr/local/lib/python3.10/site-packages (from deepchem) (2023.3.1)
Requirement already satisfied: python-dateutil>=2.8.2 in /usr/local/lib/python3.10/site-packages (from pandas->d
eepchem) (2.8.2)
Requirement already satisfied: pytz>=2020.1 in /usr/local/lib/python3.10/site-packages (from pandas->deepchem) (
2023.3)
Requirement already satisfied: tzdata>=2022.1 in /usr/local/lib/python3.10/site-packages (from pandas->deepchem)
(2023.3)
Requirement already satisfied: Pillow in /usr/local/lib/python3.10/site-packages (from rdkit->deepchem) (9.5.0)
Requirement already satisfied: threadpoolctl>=2.0.0 in /usr/local/lib/python3.10/site-packages (from scikit-lear
n->deepchem) (3.1.0)
Requirement already satisfied: six>=1.5 in /usr/local/lib/python3.10/site-packages (from python-dateutil>=2.8.2-
>pandas->deepchem) (1.16.0)
WARNING: Running pip as the 'root' user can result in broken permissions and conflicting behaviour with the syst
em package manager. It is recommended to use a virtual environment instead: https://pip.pypa.io/warnings/venv

!conda install -c conda-forge pdbfixer

Collecting package metadata (current_repodata.json): - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \

| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - done
Solving environment: | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ done

# All requested packages already installed.

!conda install -c conda-forge vina

Collecting package metadata (current_repodata.json): - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \

| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ done
Solving environment: / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / done

# All requested packages already installed.

Protein-ligand complex data

It is really helpful to visualize proteins and ligands when doing docking. Unfortunately, Google Colab doesn't currently
support the Jupyter widgets we need to do that visualization. Install MDTraj and nglview on your local machine to
view the protein-ligand complexes we're working with.

!pip install -q mdtraj nglview

# !jupyter-nbextension enable nglview --py --sys-prefix # for jupyter notebook
# !jupyter labextension install nglview-js-widgets # for jupyter lab

import os
import numpy as np
import pandas as pd

import tempfile

from rdkit import Chem

from rdkit.Chem import AllChem
import deepchem as dc

from deepchem.utils import download_url, load_from_disk

Skipped loading modules with pytorch-geometric dependency, missing a dependency. No module named 'torch_geometri
c'
Skipped loading modules with pytorch-geometric dependency, missing a dependency. cannot import name 'DMPNN' from
'deepchem.models.torch_models' (/usr/local/lib/python3.10/site-packages/deepchem/models/torch_models/__init__.py
)
Skipped loading modules with pytorch-lightning dependency, missing a dependency. No module named 'pytorch_lightn
ing'
Skipped loading some Jax models, missing a dependency. No module named 'haiku'

To illustrate the docking procedure, here we'll use a csv that contains SMILES strings of ligands as well as PDB files for
the ligand and protein targets from PDBbind. Later, we'll use the labels to train a model to predict binding affinities.
We'll also show how to download and featurize PDBbind to train a model from scratch.
data_dir = dc.utils.get_data_dir()
dataset_file = os.path.join(data_dir, "pdbbind_core_df.csv.gz")

if not os.path.exists(dataset_file):
print('File does not exist. Downloading file...')
download_url("https://s3-us-west-1.amazonaws.com/deepchem.io/datasets/pdbbind_core_df.csv.gz")
print('File downloaded...')

raw_dataset = load_from_disk(dataset_file)
raw_dataset = raw_dataset[['pdb_id', 'smiles', 'label']]

Let's see what raw_dataset looks like:

raw_dataset.head(2)

pdb_id smiles label

0 2d3u CC1CCCCC1S(O)(O)NC1CC(C2CCC(CN)CC2)SC1C(O)O 6.92

1 3cyx CC(C)(C)NC(O)C1CC2CCCCC2C[NH+]1CC(O)C(CC1CCCCC... 8.00

Fixing PDB files

Next, let's get some PDB protein files for visualization and docking. We'll use the PDB IDs from our raw_dataset and
download the pdb files directly from the Protein Data Bank using pdbfixer . We'll also sanitize the structures with
RDKit. This ensures that any problems with the protein and ligand files (non-standard residues, chemical validity, etc.)
are corrected. Feel free to modify these cells and pdbids to consider new protein-ligand complexes. We note here that
PDB files are complex and human judgement is required to prepare protein structures for docking. DeepChem includes a
number of docking utilites to assist you with preparing protein files, but results should be inspected before docking is
attempted.

from openmm.app import PDBFile

from pdbfixer import PDBFixer

from deepchem.utils.vina_utils import prepare_inputs

# consider one protein-ligand complex for visualization

pdbid = raw_dataset['pdb_id'].iloc[1]
ligand = raw_dataset['smiles'].iloc[1]

%%time
fixer = PDBFixer(pdbid=pdbid)
PDBFile.writeFile(fixer.topology, fixer.positions, open('%s.pdb' % (pdbid), 'w'))

p, m = None, None
# fix protein, optimize ligand geometry, and sanitize molecules
try:
p, m = prepare_inputs('%s.pdb' % (pdbid), ligand)
except:
print('%s failed PDB fixing' % (pdbid))

if p and m: # protein and molecule are readable by RDKit

print(pdbid, p.GetNumAtoms())
Chem.rdmolfiles.MolToPDBFile(p, '%s.pdb' % (pdbid))
Chem.rdmolfiles.MolToPDBFile(m, 'ligand_%s.pdb' % (pdbid))

<timed exec>:7: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
Warning: importing 'simtk.openmm' is deprecated. Import 'openmm' instead.
3cyx 1510
CPU times: user 2.04 s, sys: 157 ms, total: 2.2 s
Wall time: 4.32 s

Visualization
If you're outside of Colab, you can expand these cells and use MDTraj and nglview to visualize proteins and ligands.

import mdtraj as md
import nglview

from IPython.display import display, Image

Let's take a look at the first protein ligand pair in our dataset:

protein_mdtraj = md.load_pdb('3cyx.pdb')
ligand_mdtraj = md.load_pdb('ligand_3cyx.pdb')
We'll use the convenience function nglview.show_mdtraj in order to view our proteins and ligands. Note that this will
only work if you uncommented the above cell, installed nglview, and enabled the necessary notebook extensions.

v = nglview.show_mdtraj(ligand_mdtraj)

display(v) # interactive view outside Colab

NGLWidget()

Now that we have an idea of what the ligand looks like, let's take a look at our protein:

view = nglview.show_mdtraj(protein_mdtraj)
display(view) # interactive view outside Colab

NGLWidget()

Molecular Docking
Ok, now that we've got our data and basic visualization tools up and running, let's see if we can use molecular docking
to estimate the binding affinities between our protein ligand systems.

There are three steps to setting up a docking job, and you should experiment with different settings. The three things
we need to specify are 1) how to identify binding pockets in the target protein; 2) how to generate poses (geometric
configurations) of a ligand in a binding pocket; and 3) how to "score" a pose. Remember, our goal is to identify
candidate ligands that strongly interact with a target protein, which is reflected by the score.

DeepChem has a simple built-in method for identifying binding pockets in proteins. It is based on the convex hull
method. The method works by creating a 3D polyhedron (convex hull) around a protein structure and identifying the
surface atoms of the protein as the ones closest to the convex hull. Some biochemical properties are considered, so the
method is not purely geometrical. It has the advantage of having a low computational cost and is good enough for our
purposes.

finder = dc.dock.binding_pocket.ConvexHullPocketFinder()
pockets = finder.find_pockets('3cyx.pdb')
len(pockets) # number of identified pockets

Pose generation is quite complex. Luckily, using DeepChem's pose generator will install the AutoDock Vina engine under
the hood, allowing us to get up and running generating poses quickly.

vpg = dc.dock.pose_generation.VinaPoseGenerator()

We could specify a pose scoring function from deepchem.dock.pose_scoring , which includes things like repulsive and
hydrophobic interactions and hydrogen bonding. Vina will take care of this, so instead we'll allow Vina to compute scores
for poses.

!mkdir -p vina_test

%%time
complexes, scores = vpg.generate_poses(molecular_complex=('3cyx.pdb', 'ligand_3cyx.pdb'), # protein-ligand files for
out_dir='vina_test',
generate_scores=True
)

CPU times: user 41min 4s, sys: 21.9 s, total: 41min 26s
Wall time: 28min 32s
/usr/local/lib/python3.10/site-packages/vina/vina.py:260: DeprecationWarning: `np.int` is a deprecated alias for
the builtin `int`. To silence this warning, use `int` by itself. Doing this will not modify any behavior and is
safe. When replacing `np.int`, you may wish to use e.g. `np.int64` or `np.int32` to specify the precision. If yo
u wish to review your current use, check the release note link for additional information.
Deprecated in NumPy 1.20; for more details and guidance: https://numpy.org/devdocs/release/1.20.0-notes.html#dep
recations
self._voxels = np.ceil(np.array(box_size) / self._spacing).astype(np.int)

We used the default value for num_modes when generating poses, so Vina will return the 9 lowest energy poses it found
in units of kcal/mol .

scores

[-9.484, -9.405, -9.195, -9.151, -8.9, -8.696, -8.687, -8.633, -8.557]

Can we view the complex with both protein and ligand? Yes, but we'll need to combine the molecules into a single RDkit
molecule.

complex_mol = Chem.CombineMols(complexes[0][0], complexes[0][1])

Let's now visualize our complex. We can see that the ligand slots into a pocket of the protein.

v = nglview.show_rdkit(complex_mol)
display(v)

NGLWidget()

Now that we understand each piece of the process, we can put it all together using DeepChem's Docker class. Docker
creates a generator that yields tuples of posed complexes and docking scores.

docker = dc.dock.docking.Docker(pose_generator=vpg)
posed_complex, score = next(docker.dock(molecular_complex=('3cyx.pdb', 'ligand_3cyx.pdb'),
use_pose_generator_scores=True))

Modeling Binding Affinity

Docking is a useful, albeit coarse-grained tool for predicting protein-ligand binding affinities. However, it takes some
time, especially for large-scale virtual screenings where we might be considering different protein targets and
thousands of potential ligands. We might naturally ask then, can we train a machine learning model to predict docking
scores? Let's try and find out!
We'll show how to download the PDBbind dataset. We can use the loader in MoleculeNet to get the 4852 protein-ligand
complexes from the "refined" set or the entire "general" set in PDBbind. For simplicity, we'll stick with the ~100
complexes we've already processed to train our models.

Next, we'll need a way to transform our protein-ligand complexes into representations which can be used by learning
algorithms. Ideally, we'd have neural protein-ligand complex fingerprints, but DeepChem doesn't yet have a good
learned fingerprint of this sort. We do however have well-tuned manual featurizers that can help us with our challenge
here.

We'll make use of two types of fingerprints in the rest of the tutorial, the CircularFingerprint and
ContactCircularFingerprint . DeepChem also has voxelizers and grid descriptors that convert a 3D volume
containing an arragment of atoms into a fingerprint. These featurizers are really useful for understanding protein-ligand
complexes since they allow us to translate complexes into vectors that can be passed into a simple machine learning
algorithm. First, we'll create circular fingerprints. These convert small molecules into a vector of fragments.

pdbids = raw_dataset['pdb_id'].values
ligand_smiles = raw_dataset['smiles'].values

%%time
for (pdbid, ligand) in zip(pdbids, ligand_smiles):
fixer = PDBFixer(url='https://files.rcsb.org/download/%s.pdb' % (pdbid))
PDBFile.writeFile(fixer.topology, fixer.positions, open('%s.pdb' % (pdbid), 'w'))

p, m = None, None
# skip pdb fixing for speed
try:
p, m = prepare_inputs('%s.pdb' % (pdbid), ligand, replace_nonstandard_residues=False,
remove_heterogens=False, remove_water=False,
add_hydrogens=False)
except:
print('%s failed sanitization' % (pdbid))

if p and m: # protein and molecule are readable by RDKit

Chem.rdmolfiles.MolToPDBFile(p, '%s.pdb' % (pdbid))
Chem.rdmolfiles.MolToPDBFile(m, 'ligand_%s.pdb' % (pdbid))

<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:11:45] UFFTYPER: Unrecognized atom type: S_5+4 (7)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
3cyx failed sanitization
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:12:02] UFFTYPER: Warning: hybridization set to SP3 for atom 17
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:12:04] UFFTYPER: Warning: hybridization set to SP3 for atom 6
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:12:06] UFFTYPER: Warning: hybridization set to SP3 for atom 1
[15:12:06] UFFTYPER: Unrecognized atom type: S_5+4 (21)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:12:23] UFFTYPER: Warning: hybridization set to SP3 for atom 20
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:12:31] UFFTYPER: Warning: hybridization set to SP3 for atom 19
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:12:35] UFFTYPER: Warning: hybridization set to SP3 for atom 29
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:13:03] UFFTYPER: Unrecognized atom type: S_5+4 (39)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:13:37] UFFTYPER: Warning: hybridization set to SP3 for atom 33
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:01] UFFTYPER: Unrecognized atom type: S_5+4 (11)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:02] UFFTYPER: Unrecognized atom type: S_5+4 (47)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:14] UFFTYPER: Unrecognized atom type: S_5+4 (1)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:27] UFFTYPER: Warning: hybridization set to SP3 for atom 6
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:33] UFFTYPER: Unrecognized atom type: S_5+4 (47)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:43] UFFTYPER: Unrecognized atom type: S_5+4 (28)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:55] UFFTYPER: Warning: hybridization set to SP3 for atom 17
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:14:57] UFFTYPER: Warning: hybridization set to SP3 for atom 6
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:08] Explicit valence for atom # 388 O, 3, is greater than permitted
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:15] UFFTYPER: Warning: hybridization set to SP3 for atom 9
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:19] UFFTYPER: Unrecognized atom type: S_5+4 (6)
3utu failed sanitization
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:29] UFFTYPER: Unrecognized atom type: S_5+4 (1)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:39] UFFTYPER: Unrecognized atom type: S_5+4 (19)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:43] UFFTYPER: Unrecognized atom type: S_5+4 (21)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:15:57] UFFTYPER: Unrecognized atom type: S_5+4 (9)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:16:01] UFFTYPER: Warning: hybridization set to SP3 for atom 18
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:16:21] UFFTYPER: Warning: hybridization set to SP3 for atom 17
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:16:42] UFFTYPER: Warning: hybridization set to SP3 for atom 10
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:17:19] UFFTYPER: Unrecognized atom type: S_5+4 (13)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:17:25] UFFTYPER: Unrecognized atom type: S_5+4 (10)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:17:27] UFFTYPER: Unrecognized atom type: S_5+4 (6)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:17:28] UFFTYPER: Warning: hybridization set to SP3 for atom 11
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:17:46] UFFTYPER: Unrecognized atom type: S_5+4 (8)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:17:58] UFFTYPER: Unrecognized atom type: S_5+4 (4)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:18:02] UFFTYPER: Unrecognized atom type: S_5+4 (9)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:18:15] UFFTYPER: Unrecognized atom type: S_5+4 (1)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:18:32] UFFTYPER: Unrecognized atom type: S_5+4 (23)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:18:35] UFFTYPER: Unrecognized atom type: S_5+4 (22)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:18:42] UFFTYPER: Warning: hybridization set to SP3 for atom 8
[15:18:42] UFFTYPER: Warning: hybridization set to SP3 for atom 24
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:01] UFFTYPER: Warning: hybridization set to SP3 for atom 16
[15:19:01] UFFTYPER: Unrecognized atom type: S_5+4 (20)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:02] UFFTYPER: Unrecognized atom type: S_5+4 (6)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:05] UFFTYPER: Unrecognized atom type: S_5+4 (6)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
1hfs failed sanitization
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:22] UFFTYPER: Warning: hybridization set to SP3 for atom 20
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:41] Explicit valence for atom # 1800 C, 5, is greater than permitted
[15:19:41] UFFTYPER: Unrecognized atom type: S_5+4 (11)
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:42] UFFTYPER: Warning: hybridization set to SP3 for atom 11
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:57] UFFTYPER: Warning: hybridization set to SP3 for atom 9
[15:19:57] UFFTYPER: Warning: hybridization set to SP3 for atom 23
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
[15:19:59] UFFTYPER: Warning: hybridization set to SP3 for atom 8
[15:19:59] UFFTYPER: Warning: hybridization set to SP3 for atom 12
[15:19:59] UFFTYPER: Warning: hybridization set to SP3 for atom 34
[15:19:59] UFFTYPER: Warning: hybridization set to SP3 for atom 41
<timed exec>:8: DeprecationWarning: Call to deprecated function prepare_inputs. Please use the corresponding fun
ction in deepchem.utils.docking_utils.
CPU times: user 4min 9s, sys: 3.31 s, total: 4min 12s
Wall time: 8min 19s

proteins = [f for f in os.listdir('.') if len(f) == 8 and f.endswith('.pdb')]

ligands = [f for f in os.listdir('.') if f.startswith('ligand') and f.endswith('.pdb')]

We'll do some clean up to make sure we have a valid ligand file for every valid protein. The lines here will compare the
PDB IDs between the ligand and protein files and remove any proteins that don't have corresponding ligands.

# Handle failed sanitizations

failures = set([f[:-4] for f in proteins]) - set([f[7:-4] for f in ligands])
for pdbid in failures:
proteins.remove(pdbid + '.pdb')
len(proteins), len(ligands)

(190, 190)

pdbids = [f[:-4] for f in proteins]

small_dataset = raw_dataset[raw_dataset['pdb_id'].isin(pdbids)]
labels = small_dataset.label

fp_featurizer = dc.feat.CircularFingerprint(size=2048)

features = fp_featurizer.featurize([Chem.MolFromPDBFile(l) for l in ligands])

dataset = dc.data.NumpyDataset(X=features, y=labels, ids=pdbids)

train_dataset, test_dataset = dc.splits.RandomSplitter().train_test_split(dataset, seed=42)

The convenience loader dc.molnet.load_pdbbind will take care of downloading and featurizing the pdbbind dataset
under the hood for us. This will take quite a bit of time and compute, so the code to do it is commented out. Uncomment
it and grab a cup of coffee if you'd like to featurize all of PDBbind's refined set. Otherwise, you can continue with the
small dataset we constructed above.

# # Uncomment to featurize all of PDBBind's "refined" set

# pdbbind_tasks, (train_dataset, valid_dataset, test_dataset), transformers = dc.molnet.load_pdbbind(
# featurizer=fp_featurizer, set_name="refined", reload=True,
# data_dir='pdbbind_data', save_dir='pdbbind_data')

Now, we're ready to do some learning!

To fit a deepchem model, first we instantiate one of the provided (or user-written) model classes. In this case, we have a
created a convenience class to wrap around any ML model available in Sci-Kit Learn that can in turn be used to
interoperate with deepchem. To instantiate an SklearnModel , you will need (a) task_types, (b) model_params, another
dict as illustrated below, and (c) a model_instance defining the type of model you would like to fit, in this case a
RandomForestRegressor .

from sklearn.ensemble import RandomForestRegressor

from deepchem.utils.evaluate import Evaluator

import pandas as pd

seed = 42 # Set a random seed to get stable results

sklearn_model = RandomForestRegressor(n_estimators=100, max_features='sqrt')
sklearn_model.random_state = seed
model = dc.models.SklearnModel(sklearn_model)
model.fit(train_dataset)

Note that the R 2

value for the test set indicates that the model isn't producing meaningful outputs. It turns out that predicting binding
affinities is hard. This tutorial isn't meant to show how to create a state-of-the-art model for predicting binding affinities,
but it gives you the tools to generate your own datasets with molecular docking, featurize complexes, and train models.

# use Pearson correlation so metrics are > 0

metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)

evaluator = Evaluator(model, train_dataset, [])

train_r2score = evaluator.compute_model_performance([metric])
print("RF Train set R^2 %f" % (train_r2score["pearson_r2_score"]))

evaluator = Evaluator(model, test_dataset, [])

test_r2score = evaluator.compute_model_performance([metric])
print("RF Test set R^2 %f" % (test_r2score["pearson_r2_score"]))

RF Train set R^2 0.888697

RF Test set R^2 0.007797

We're using a very small dataset and an overly simplistic representation, so it's no surprise that the test set
performance is quite bad.

# Compare predicted and true values

list(zip(model.predict(train_dataset), train_dataset.y))[:5]

[(6.862549999999994, 7.4),
(6.616400000000008, 6.85),
(4.852004999999995, 3.4),
(6.43060000000001, 6.72),
(8.66322999999999, 11.06)]

list(zip(model.predict(test_dataset), test_dataset.y))[:5]
[(5.960549999999999, 4.21),
(6.051305714285715, 8.7),
(5.799900000000003, 6.39),
(6.433881666666665, 4.94),
(6.7465399999999995, 9.21)]

The protein-ligand complex view.

In the previous section, we featurized only the ligand. This time, let's see if we can do something sensible with our
protein-ligand fingerprints that make use of our structural information. To start with, we need to re-featurize the dataset
but using the contact fingerprint this time.

fp_featurizer = dc.feat.ContactCircularFingerprint(size=2048)

features = fp_featurizer.featurize(zip(ligands, proteins))

dataset = dc.data.NumpyDataset(X=features, y=labels, ids=pdbids)
train_dataset, test_dataset = dc.splits.RandomSplitter().train_test_split(dataset, seed=42)

[15:21:40] Explicit valence for atom # 3 C, 5, is greater than permitted

Mol [H]OC([H])([H])[C@]1([H])O[C@@]2([H])SC([H])([H])(N([H])C([H])([H])C([H])([H])[H])N([H])[C@@]2([H])[C@@]([H]
)(O[H])[C@]1([H])O[H] failed sanitization
[15:21:47] Explicit valence for atom # 214 O, 3, is greater than permitted
Mol CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CN
C3=C2C=CC=C3)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H
]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H]2
CCCN2C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=
O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)
NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H]2CSSC[C@H](NC(=O
)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]3CCCN
3C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[
C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCC(N)=O)NC(=O)CN)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(
=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@
H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=
O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N2)CSSC[C@@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@
H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)NCC(=O)N[C@@H](CC
2=CC=CC=C2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@H](C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=CC=C
2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CNC3=C2C=CC
=C3)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@
H](CCC(N)=O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N2C3C(=O)O32)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)NC(=O)CNC
(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC1=O.CC[C@H](C)[C@H](
NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@]12C(CC(=O)O)C13C(C)[C@H](
N)C(=O)N32)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H]
(CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(
=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C
)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CC=C(O)C=C2
)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[
C@@H](CC(N)=O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=
O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](
CCCCN)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@H]2CCCN(C(=N)N)C(C(=O
)O)C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=
O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C
@H](C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](C(=O)N[C@@H](CC3=CNC=N3)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCNC(=N)N)C(=
O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@
@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](
CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)
C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N3CCC[C@H]3C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)
N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](C(=O)N[C@@H](CC3=CNC=N3)C(=O)N3CCC[C@H]
3C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)N)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](
CCCNC(=N)N)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCC
N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]
(CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)
N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@]34C(=O)O3C4C3=CC=C(O)C=C3)[C@@H](C)O)C(=O)N[C@@H
](CC(C)C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C
@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]
(C)C(=O)NCC(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@H]
(C(=O)NCC(=O)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)
N[C@H](C=O)CCC(=O)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@
H](C)CC)[C@@H](C)CC)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC2=O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)NC(=O)[C@H](CC2=CN
C=N2)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC2=CNC
3=C2C=CC=C3)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(C)C
)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CNC1=O)C(C)C.CC[C@H](C)[C@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O
)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](N)CC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@
H](CO)CC1CCC(OS(O)(O)O)CC1.CO[C@H]1CC[C@H](S(O)(O)N[C@@H](C[C@@H](O)NC[C@H]2CC[C@H](CN)CC2)C(O)N2CCC[C@H]2[C@H](
O)NCC2CCC(C(N)N)CC2)CC1Cl.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.[NaH].[NaH] failed sanitization
[15:21:58] Explicit valence for atom # 9 C, 5, is greater than permitted
Mol [H]O[C@@]1([H])[C@@]([H])(O[H])[C@@]2([H])N([C@@]([H])(O[H])[C@]1([H])O[H])C([H])([H])(N([H])C([H])([H])C([H
])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])OC2([H])[H] failed sanitization
[15:22:27] Explicit valence for atom # 5358 O, 3, is greater than permitted
Mol CC(O)O.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@@H]1CC(O)=OO=C([C@H](CCCCN)NC(=
O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C
@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](C)N
C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@
@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=
C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)
[C@H](C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC
2=CNC=N2)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3
)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C
@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(
=O)O)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@
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=C1)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)
C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(
=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O
)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C
=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](
C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@
@H](C)C=O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C.CC[C@H](C)[C@H](NC(=O)CN
C(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=
C2)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=
O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO
)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)N)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CC1=CC=C(O
)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O
)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]
(CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C
@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1
=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)
O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(=O)O)C
(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](
CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@H](C(=O)N
CC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C
@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@
@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC
=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@
H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)
NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC
=C1)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC
1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)
N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C
(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=
O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC
C(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)
[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC.CC[C@H](C)[
C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1
=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@H
](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)N
C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)N)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(=O)N[C@@
H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@
H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1
)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)
C=C1)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=
O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[
C@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@
H](CC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C
(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N
[C@H](C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H
](C)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C
)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@@H](CC1
=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=
O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CC
C(=O)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@
H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=
O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCN
C(=N)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=C
C=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=
O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=
O)O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](
C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OCCO.OC[C@H]1NC(
NO)[C@H](O)[C@@H](O)[C@@H]1O.OC[C@H]1NC(NO)[C@H](O)[C@@H](O)[C@@H]1O.[CaH2].[CaH2].[CaH2] failed sanitization
[15:23:08] Explicit valence for atom # 4247 O, 3, is greater than permitted
Mol CC(C)C(O)N[C@H]1C2NC(CCC3CCCCC3)CN2[C@H](CO)[C@@H](O)[C@@H]1O.CC(C)C(O)N[C@H]1C2N[C@@H](CCC3CCCCC3)CN2[C@H](
CO)[C@@H](O)[C@@H]1O.CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=
O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)N
C(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](
CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O
)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@
H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O
)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](
CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H
](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)
C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O
)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)
NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)
C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[
C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C
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NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)N
C(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N
)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H]
(CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](
CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC
CCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O
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CN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C
C(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CO)NC
(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC
(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)
NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)
NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(
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(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)CNC(=
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[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C
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C(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C
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NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H
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C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N
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CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CC=
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(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)
N)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O
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[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C
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NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C
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N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=C
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(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(
=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C
@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC
(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=
O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=
O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C
C(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C
@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](
CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)
[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H
]1CCCN1C(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN
1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(N)=O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C
)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@
H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)
[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C
@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C
@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@
H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC
)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[
C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@
@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(=O)O.Cl.Cl.Cl.Cl.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O failed sanitization
[15:23:10] Explicit valence for atom # 2174 O, 3, is greater than permitted
Mol CC(C)[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)N)C(=O)N[C@@H](CO)C(=O)N1O2C(=O)[C@]12C.CC[C@H](C)[C@H](NC(=O)CNC(=O
)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](C)
NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[
C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCC
N1C(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCC
N1C(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@
H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@
H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@
H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCN
C(=N)N)NC(=O)[C@H](CC1=CNC=N1)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=
O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)
[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H](NC(
=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(N)=O)[C@@H](C)CC)[C@@H](C)C
C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[
C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=
O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]
(CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC
(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N
[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@
@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O
)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]
(CCSC)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N
[C@H](C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](
CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@
H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](
C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C
)C)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(=O)O)
C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(N)=O)C
(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N
[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C
2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC
=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](
CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[
C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCCN)C
(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@
H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC
(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H
](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N
[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@]1(C)OC1=O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)
O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O
)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC.CC[C@H](C)[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](
NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(
=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O
)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)
CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)
[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C
@@H]1CCCN1C(=O)[C@@H](N)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@H](C(=O)N
[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C=O)CCCCN)C(C)C.CN[C@@H]1C[C@H]2O[C@@](C)([C@@H]1OC)N1C3CCCCC3C3C4C
(C(O)N[C@@H]4O)C4C5CCCCC5N2C4C31.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OS(O)(O)O failed sanitization
[15:23:15] Explicit valence for atom # 1823 O, 4, is greater than permitted
Mol CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H]1CSSC[C@@
H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O
)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=
O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@H]2CSSC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]
(CC3=CC=C(O)C=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC
3=CC=CC=C3)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N
[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(
=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC3=CNC=N
3)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN
)C(=O)N[C@@H](CC3=CNC=N3)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@H](C(=O
)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](
CC3=CC=CC=C3)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(
=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N3CCC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC3
=CC=CC=C3)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N3CCC[C
@H]3C(=O)N[C@@H](C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H]3CCCN3C(=O)CN
C(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](CSSC[C@H](NC(=O)[C@H
](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](N)CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@
@H](CC4=CC=CC=C4)C(=O)N[C@H](C=O)CSSC[C@H](N)C(=O)N[C@H](C=O)CO)NC(=O)[C@@H](NC(=O)[C@@H](N)C(C)C)C(C)C)C(=O)N[C
@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@@H](CC4=CC=C(O)C=C4)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C
(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N3)[C@@H](
C)CC)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC
(=O)O)C(N)=O)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N
[C@@H](CC(=O)O)C(=O)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@H](
C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(
=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC3=CC=CC=C3)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H
](C(=O)N[C@@H](CC3=CNC=N3)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC
(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC
SC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H
](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@H]3CSSC[C@@H](C(=O)
N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC4=CC=C(O)C=C4)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C
CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H]4CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C
@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC5=CC=C(O)C=C5)C(=O)NCC(=O)N[C@H](C(=
O)N[C@@H](CC5=CC=C(O)C=C5)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC5
=CC=CC=C5)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC5=CNC6=C5C=CC=C6)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)
O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C5=O6N7CC8O=C9%10%11[N+]%12%13O%14=C(O)C%14%129%15C%109(NC(=O)[C@H](CC
CCN)NC(=O)[C@]%10(CCSC)N5N%10C76=N)[C@@](C)(O)C8%139%11%15)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)N
C(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC5=CNC6=C5C=CC=C6)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C
@@H](C)CC)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CC5=CC=C(O)C=C5)N
C(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CCCNC(=N)N)NC(=
O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC5=CNC=N5)NC(=O)[C@@H]5CCCN5C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)
[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC4=O)[C@@H](C)O)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CCSC)NC(=O)[C@H]
(CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H]
(CC4=CC=CC=C4)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC3=O)C(C)C)C(C)
C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C
)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)NC(=O)[C@H
](CC3=CNC=N3)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O
)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@
H]([C@@H](C)CC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)CNC2=O)[C@@H](C)CC)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](CCCCN)NC1=O)C(C)C.N=C(N)NCCCCC(=O)O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OC1CCCCN1C1CCC(N[C@@H](O)[C@H]2CN(CC(F)F)C[C@@H]
2[C@@H](O)N[C@H]2CC[C@@H](Cl)CN2)[C@@H](F)C1.[CaH2].[NaH] failed sanitization
[15:23:56] Explicit valence for atom # 6175 O, 3, is greater than permitted
Mol Br.Br.Br.Br.Br.Br.Br.Br.Br.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[
C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@
H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@
H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C
C1=CNC=N1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O
)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(N)=O)
NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)
C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C
@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(
=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[
C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1
C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C
@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](
CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=
C1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](CCC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)
C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)
[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC
C(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C
CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C
@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@
H](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O
)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@
H](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](
CCC(=O)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[
C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C
@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC
(=O)[C@@H](N)CC(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H]
(C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[
C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@H](C(=O)N
[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@H]
(C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)
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C(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCSC)NC1=O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[
C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C
(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@
H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)
[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[
C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)
O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H
](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(C)C.CC[C@H](C)[C@
H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O
)[C@@H](N)CC(C)C)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC
=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)O)[C@@H](C)O.Cl.Cl.Cl.Cl.Cl.Cl.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCC
O.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.
OC[C@H]1C[C@@H]2[C@@H](O)[C@@H](O)[C@@]1(O)CN2CC1CCCCC1.OC[C@H]1C[C@@H]2[C@@H](O)[C@@H](O)[C@@]1(O)CN2CC1CCCCC1
failed sanitization
[15:24:08] Explicit valence for atom # 1064 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](
NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)
[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@
H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)
[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](
NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](C)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)
NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC
(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O
)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](
CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C
)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O
)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(
C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](
CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H
](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)
[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)
NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@
@H](NC(=O)[C@@H](N)CC(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)
C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)C
C)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C
)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C
(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC=N1)C1=OO1.CC[C@H](C)[C@H](NC(=O)CNC
(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC
(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=
N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=
O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)
NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@
H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[
C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)N
C(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](
C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O
)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[
C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C
CCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC(C)C
)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O
)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H
](CC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H
](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O
)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O
)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)[C@
@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@
@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)C
C)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N
[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@
H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC=N1)C1=OO1.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O
)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO
)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(
=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC
(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=
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(O)[C@@H]1O)NC1CCCCC1.OC(CCC1C[C@@](O)(C(O)O)C[C@@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](O)
[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](
O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H
](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@
@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[
C@@H](O)[C@@H]1O)NC1CCCCC1.OC(CC[C@@H]1C[C@@](O)(C(O)O)C[C@@H](O)[C@@H]1O)NC1CCCCC1.OC(O)[C@]1(O)C[C@@H](CC[C@H]
(O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)C[C@@
H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@
]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C
1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O
)[C@H](O)C1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC2)[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)C[C@@H](CC[C@H](O)NC2CCCCC
2)[C@@H](O)[C@H](O)C1 failed sanitization
[15:24:10] Explicit valence for atom # 11 C, 5, is greater than permitted
Mol [H]O[C@]1([H])C([H])([H])C([H])([H])N2[C@@]1([H])[C@@]([H])(C(F)(F)F)OC2([H])([H])N([H])[C@]1([H])C([H])([H]
)C([H])([H])[C@@]([H])(C([H])([H])N([H])[H])[C@@]([H])(Cl)[C@@]1([H])C([H])([H])[H] failed sanitization
[15:24:41] Explicit valence for atom # 148 O, 3, is greater than permitted
Mol CC[C@@H](C)[C@@H]1NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
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O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC2=NN2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[
C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)N
C(=O)[C@H](CCSC)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CCSC)NC(=O)[
C@H](CCCCN)NC(=O)[C@H]2CC(O)=O3N2C3(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](C)NC(=O)[C@@H](NC(=O)[C@H](C
CCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CC=CC
=C2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O
)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H
]([C@@H](C)O)N2C(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C
CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)CNC(
=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CN
C(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCCN)NC
(=O)[C@H](CO)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=
O)[C@H](CC(C)C)NC(=O)[C@@H]3CCCN3C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)
[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)
O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@@H](NC
(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O
)[C@H](C)NC(=O)CNC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H](NC(
=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CCCCN)NC(=O)
[C@H](CC3=CC=CC=C3)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@@H](NC(
=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CS
)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CCCNC(=N)N)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H
](CCC(=O)O)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CC(N)=O)NC(=O)C(CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@
H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H
](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@]3
(N)CC3CCN)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@
H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C
)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)CC2C(N)=O)C2CC(=O)O2)[C@@H](C)CC)[
C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H
](C)O)[C@@H](C)CC)CSSC[C@@H](C=O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C
C2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(
C)C)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC
(=O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)
[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCCN)NC(
=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC1=O.C[C@@H]1ONC(O)[C@@H]1C[C@H](N)C(O)O.C[C@@H]1ONC(O)[C@@H
]1C[C@H](N)C(O)O.C[C@H]1ONC(O)[C@@H]1C[C@H](N)C(O)O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.[Zn].[Zn].[Zn].[Zn].[Zn] failed sanitization
[15:24:46] Explicit valence for atom # 282 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O
)[C@H](CCSC)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C
@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)N
C(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@
H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O
)[C@H](CCSC)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
(CO)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)
[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC1
=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H]
(CO)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)CNC
(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H]
(CCCCN)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C
)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H
]1CCCN1C(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C
@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1
)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1
=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC
(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)N
C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](
CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=
O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)
NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CS)NC(=O)[
C@H](CC(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O
)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(C)C)
NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CC(
C)C)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)
CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@
@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)CNC(=O)[C@H](C
C2=CC=CC=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](CC2=CNC=N2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)
[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=
O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CCC(=O)
O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H]
(CC(C)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C
CCNC(=N)N)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](
CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=C(O)C
=C2)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(N)=O)NC
(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)
[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)CNC(=O)CNC(=O)[
C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=
O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN
2C(=O)[C@H](CO)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(
=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)
[C@H](CC(N)=O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H]
(CC(=O)N[C@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3NC(C)O)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@@H](NC(=O)CNC(=O)[
C@H](CO)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]3CCCN3C(
=O)[C@H](CCC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)
[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC3=ON3)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN3C(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)
NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CO)NC(=O)[
C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)
CNC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H
](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CO)C(C)C)[C@@H]
(C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@
@H](CCC(N)=O)C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C
@@H](CCC(N)=O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N3CCC[C@H]3C(=O)NCC(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CO)C(=O)NC
C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)N[C@@H](CC(N)=O)C(=
O)N3CCC[C@H]3C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C
O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N2)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](
C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@
@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C
C(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC2=OO2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O
)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N1)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC
)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CCCCN)
C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)
O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](
CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)
[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN1NC1=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@
@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC
(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=
O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)N
C(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CO)[C@@H](C)O)[C@@H](C)O)[C@@H](
C)CC)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C
C(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(
=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@]1([C@@H](C)O)OC1=O)C(C)C)C(=
O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H]
(C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H
](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CC(=O)N[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1NC(C)O)C(=O)NCC(=O)N[C@H](C(=O
)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]
(CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C
O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N1CCC[C@H]1C(=O)N[C@
@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=C
NC=N1)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C
C1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C
)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=
CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[
C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C
@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(
=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(N)=O)C(
=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[
C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C
@@H](C)CC.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OC1CC[C@H]2C
(CCC[C@@H]2NCCCCCCCCCCCCN[C@H]2CCCC3N[C@H](O)CCC32)N1 failed sanitization
[15:25:02] Explicit valence for atom # 8 C, 5, is greater than permitted
Mol CC(C)C[C@H](N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=
O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C=O)CC1=CC=CC=C1)[C@@H](C)O)C(C)C)[C@@H](C)O.CC(C)
C[C@H](N)C(=O)N[C@H](C=O)CO.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(
=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1C2=OO21)NC
(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C
)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](
C)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)N
C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC
(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC
(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(
=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(C
)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]
(NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)N
C(=O)[C@@H](N)CCSC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[
C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C
C(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C
(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)
N[C@H](C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)
C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=
O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N
[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO
)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C
@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H
](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=
O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C
CCNC(=N)N)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O
)O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@
@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@
@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[
C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C
CCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C
)C)C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(
=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C
@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[
C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC
(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC
(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CCC(
=O)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@
@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@
H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C
@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](
CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=
O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=C(O)C=
C1)C(=O)N[C@]1(CC2=CC=CC=C2)OC1=O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](
C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C
(C)C)C(C)C)C(C)C)[C@@H](C)CC)C(C)C.CC[C@H](C)[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(
=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C
C1=CNC=N1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC
(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@
H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[
C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]1C
CCN1C(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)
NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@]1(CCCNC(=N)N)NC23=O45N(CCC[C@H](N)C(=O)N6CCC[C@H]6C(=O)N[C@@H](CCCNC(
=N)N)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC6=CC=CC=C6)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)C
C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C
@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C
(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@H]2CCCCN)C4(N)=N315)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)
O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC
CCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C
C1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)
N)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N
CC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C=O)CCSC)C(C)C)[C@@H](C)O)[C@@H](C)C
C.NC1N[C@@H](O)C2C[C@H](N)CC[C@@H]2N1.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.[Zn] failed sanitization
[15:25:11] Explicit valence for atom # 1849 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](N)C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H]1CSSC[C@@
H](C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O
)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=
O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@H]2CSSC[C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]
(CC3=CC=C(O)C=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC
3=CC=CC=C3)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N
[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(
=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC3=CNC=N
3)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN
)C(=O)N[C@@H](CC3=CNC=N3)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@H](C(=O
)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](
CC3=CC=CC=C3)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(
=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N3CCC[C@H]3C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC3
=CC=CC=C3)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N3CCC[C
@H]3C(=O)N[C@@H](C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H]3CCCN3C(=O)CN
C(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@H](CO)NC(=O)[C@@H]4CSSC[C@@H]5NC(=O)[C
@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)
[C@H](CC(C)C)NC(=O)[C@@H](N)CCCCN)CSSC[C@H](NC(=O)[C@H](CC6=CC=CC=C6)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(=O)O)NC
5=O)C(=O)N[C@@H](CC5=CNC=N5)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)
=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N4)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC
(=O)N[C@@H](CC4=CC=C(O)C=C4)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O
)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N3)[C@@H](C)CC)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC
CN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@
@H](CCCNC(=N)N)C(=O)O)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N
)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=
O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](
C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC3=CC=CC=C3)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C
(=O)N[C@H](C(=O)N[C@@H](CC3=CNC=N3)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[
C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N
[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC3=CC=C(O)C=C3)C
(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@H]3CSSC[C@
@H](C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC4=CC=C(O)C=C4)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)
N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H]4CSSC[C@@H](C(=O)N[C@@H](C
)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC5=CC=C(O)C=C5)C(=O)NCC(=O)N
[C@H](C(=O)N[C@@H](CC5=CC=C(O)C=C5)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[
C@@H](CC5=CC=CC=C5)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC5=CNC6=C5C=CC=C6)C(=O)N[C@H](C(=O)N[C@@
H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@]5([C@@H](C)O)C
6=OO65)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC5=CN
C6=C5C=CC=C6)NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](
C(C)C)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CC5=CC=C(O)C=C5)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H
](CCCCN)NC(=O)[C@H](CC5=CC=CC=C5)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC5
=CNC=N5)NC(=O)[C@@H]5CCCN5C(=O)CNC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC4=O)[C@@
H](C)O)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]([C@@H](C)O
)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC4=CC=CC=C4)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C
@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC3=O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O
)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)
CC)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H]
([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CC3=CC=CC=C3)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)C
NC2=O)[C@@H](C)CC)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC1=O)C(C)C.C[N+](C)(C)CCCN1
C(O)[C@@H]2[C@H](C1O)[C@H](C1CO[C@@H]([C@H]3CCC(Cl)S3)N1)N1CCC[C@@H]21.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.[NaH].[NaH] failed sanitization
[15:25:21] Explicit valence for atom # 681 O, 3, is greater than permitted
Mol CCC1C[C@@H]2CC3NC4CC(Cl)CCC4C(N)C3[C@H](C1)C2.CCCC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](
CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(
=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=
O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O
)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@
H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)
NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](
CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N
)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
(CC(C)C)NC(=O)[C@@H]1CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N
)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCO)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(
=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](N
C(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)N
C(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)
[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@
H](NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)CNC(=O)CNC(=O)
[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@
H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC
(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2
=CNC=N2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)
[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C
)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](
CCC(N)=O)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)
[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=
O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[
C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H
](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC2=
CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O
)CNC(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](CC2=CC=C(
O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O
)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO
)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)
C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)
NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)N[C@@H]
3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3N[C@H](C)O)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)N
C(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3C4CN34)NC(=O)[C@H](CCCCN)NC(=O)[C@@H]3CCCN3C(=O)[C
@H](CCC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCCN3NC3=N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H]
(CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H]3CCCN3C(=O)[C@
H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O
)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CO)NC(=O)[C@H](
CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H]3CCCN3C(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)CNC(=
O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(
N)=O)NC(=O)[C@@H](NC(=O)[C@@]34C5C(C)C53N4C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CO)C(C)C)[C@@H](
C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@
H](CCC(N)=O)C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@
@H](CCC(N)=O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N3CCC[C@H]3C(=O)NCC(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CO)C(=O)NCC
(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)N[C@@H](CC(N)=O)C(=O
)N3CCC[C@H]3C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC3CN3C)C(=O)N[C@@H](C3C4C(=O)O43)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C
O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N2)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](
C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@
@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(=O)N[C@H]2CC(N)=ONC(=O)C[C@H](NC(=O)[C@H](CC(C)C)NC2=
O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2OC2=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@
@H]([C@@H](C)CC)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N1)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@
H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@
H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C
(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[
C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](
CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1O=C1O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCS
C)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N1C
CC[C@H]1C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@]1(C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)
N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(
N)=O)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](
CCSC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@H](C(=O
)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O
)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CNC=N
2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H]2CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC3=CC=CC=C3)C(=O
)N[C@@H](CC3=CNC4=C3C=CC=C4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CC
(C)C)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C3=OC4567=O89%10N(C(=O)[C@H](C)N
C(=O)[C@H](CC(N)=O)N3)[C@@]8([C@@H](C)O)C9(=O)[N+]%104[C@H]5C6O7)C(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(
=O)[C@H](C(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]
(CC3=CNC=N3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCC(=O)O)NC(=O)[C@
H]([C@@H](C)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC3
=CC=CC=C3)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)N
C(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3=CNC4=C3C=CC=C
4)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=CNC=
N3)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[
C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC
(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CCSC)NC(=O)[C@H]([C@
@H](C)CC)NC(=O)[C@H](CCCNC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC
C(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC3=CC=C(O)C=C
3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3O=C3O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC
(C)C)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC3=CC=CC
=C3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)CNC(=O)[
C@H](CC3=CNC=N3)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4
)NC(=O)[C@H](C3CC(O)=O3)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(
=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CC(N)=O)
NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC3
=CC=C(O)C=C3)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CC(=O)N[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3NC(C)O)NC(
=O)CNC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@H](CC
CCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CCSC)NC(=O
)[C@H](CC(C)C)NC(=O)[C@@H]3CCCN3C2=O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C
)C2C(O)=O21)C(C)C)C(C)C)[C@@H](C)CC.N.N.N.N.N.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O failed sanitization
[15:25:46] Explicit valence for atom # 4340 O, 4, is greater than permitted
Mol CC1CCCCC1S(O)(O)NC1CC(C2CCC(CN)CC2)SC1C(O)O.CC1CCCCC1S(O)(O)NC1CC(C2CCC(CN)CC2)SC1C(O)O.CC[C@H](C)[C@H](NC(=
O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)
[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC
1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC
NC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=
O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(=N)N)NC(=O
)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@
H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCC
N)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC
1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@@H]1CCC
N1C(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC1
=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=
O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)
NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(
=O)O)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O
)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N
)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(C)C)
C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@
@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C
CCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)NCC(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H
](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N
[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N
)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C
)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC
(C)C)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H
](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H]1CSSC[C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@
@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C
)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N
CC(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O
)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@H](C(=O)N
[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC2=CC=C(O)C=C
2)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@H]2C(=
O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@
H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO
)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(
=O)N[C@@H](C)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCC
CN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC
(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@H](C(=O)N2CCC
[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=
CNC3=C2C=CC=C3)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC2=CNC=N2)
C(=O)N[C@H](C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=
O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC2=CC=C(O)C
=C2)C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](
C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N
[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](C
C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)
N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)
C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H
](CS)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H]
(CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C
(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CNC=N2)C(=O)NCC(=O)N[C@@H](CC(
C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC
2=CNC=N2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](CCC(=O
)O)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@
@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@H](C(=
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C(=N)N)NC1=O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O.CC[C@H](C)[C@H]
(NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C
@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H
](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O
)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CC
CN1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H
](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(
=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H
](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(=
O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
(CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(
N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)
[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O
)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O
)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)
NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CO)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C
)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@@H](C
C1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(
=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[
C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O
)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C
(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@H](C=O)CCC(N)=O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C
@@H](C)O)C(C)C)[C@@H](C)O)C(C)C.CC[C@H](C)[C@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C
@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=
N)N)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CN
C(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C
@H](CC1=CNC=N1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C
S)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@
H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)N
C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H
](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)
[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O
)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H]
(C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=
CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CNC=N1)NC(=
O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O
)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC
CN)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@
@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=
CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CO)[C@@H](C)O)[C@@
H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(
C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=C
C=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)
N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H]
(C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C
CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@H](C=O)CCC(N)=O)C(C)C)C(C)C)[
C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O failed sanitization
[15:25:51] Explicit valence for atom # 10 C, 5, is greater than permitted
Mol [H]O[C@@]1([H])[C@]2([H])C([H])([H])[C@@]3([H])N([H])[C@@]([H])(N([H])C([H])([H])[H])N([H])[C@@]3([H])[C@@](
[H])(C([H])([H])C([H])([H])[N+]([H])([H])C([H])([H])C3([H])C([H])([H])C([H])([H])C([H])([H])C3([H])[H])[C@@]2([H
])N([H])C([H])([H])(N([H])[H])[N+]1([H])[H] failed sanitization
[15:26:01] Explicit valence for atom # 1612 C, 5, is greater than permitted
Mol CCN(CC)C(O)C1CCC(O)C(OC)C1.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H]
(NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC
(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[
C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CO)NC(
=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)
[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCCNC(=N)N
)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[
C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)N
C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](
CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O
)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)N
C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@
H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)C(C)C)[C
@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)
CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@
@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](
CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=
O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=
O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](C
C(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=C
C=CC=C1)C(=O)NCC(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[
C@@H](C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N
[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC
=N1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C
(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO
)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)NCC(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@H](
C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H
]1C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@H]
(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N
[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H]
(CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](
C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@
@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C
C1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H]
1C(C)CNCCCC234O=C256N3C452C634C5C(C(=O)O)O6O78=C5632[N+]74C18=O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](
C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H
](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)
[C@@H](C)O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O fai
led sanitization
[15:26:04] Explicit valence for atom # 4 C, 5, is greater than permitted
Mol [H]ON([H])C1([H])([H])N([H])[C@]([H])(C([H])([H])O[H])[C@@]([H])(O[H])[C@@]([H])(O[H])[C@@]1([H])O[H] failed
sanitization
[15:26:09] Explicit valence for atom # 4247 O, 3, is greater than permitted
Mol CC(O)N[C@H]1C(NOC(O)NC2CCCCC2)O[C@H](CO)[C@@H](O)[C@@H]1O.CC(O)N[C@H]1C(NOC(O)NC2CCCCC2)O[C@H](CO)[C@@H](O)[
C@@H]1O.CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=C
C=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](N
C(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[
C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(
=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC
CN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC
(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)N
C(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O
)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)
NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C
)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)
[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC
(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H]
(CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](
CS)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C
)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]
(CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)
[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H
](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C
C(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC
C(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(
=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)
[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H
](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@
H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(
=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=
O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H
](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(N)=O)NC(=O)
[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC1
=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC
(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C
)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@@H](
NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=
CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(
=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CC(C)
C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@
H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC
(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O
)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@
@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O
)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)
[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=
O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)
NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](C
CCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[
C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)CNC(=O
)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O
)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H]
(CC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H
](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](
CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=
O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=
O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)CNC(=O)
[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)
O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H
](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C
@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H
](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CC
=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N
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O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=
C1)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC
1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H
](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H
](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](
CC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)CNC(
=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)
NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)
[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(
N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C
@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)N
C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N
)N)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)
C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=
O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(N
)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O
)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)CNC(=O)[C@H](C
C1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H]
(CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)
NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]
1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[
C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC
(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)N
C(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](
NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)
NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(
=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C
@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C
@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C
@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC
(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)
[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)
NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@
H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)
[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[
C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](
NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](N)CCC(N)=O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)
O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C
)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)C
(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@
H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@
@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H
](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)
[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@
@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)
C)[C@@H](C)CC)[C@@H](C)O)C(=O)O.Cl.Cl.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O failed sanitization
[15:26:33] Explicit valence for atom # 5 C, 5, is greater than permitted
Mol CC(C)(C)OC(O)N[C@H]1CCCCCCC[C@@H]2C[C@@]2(C(O)NS(O)(O)C2CC2)N[C@H](O)[C@@H]2C[C@@H](OC(O)N3CC4CCCC(F)C4C3)CN
2C1O.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@@H]1
CCCN1C(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H
](CO)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[
C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](CO)NC(=O)CNC(=O)[C@H](CCCN1NC1=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
(CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C
@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)N
C(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)
N)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1
=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O
)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O
)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](C)NC
(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC1=CNC=N1)N
C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@
@H](NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O
)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C
@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCN1N=C1N)NC(=O
)CNC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CS
)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=
O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)
NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C
@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H
](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC12=CN1C=N2)C(C)C)C(C)C)[
C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C1CC1(N)=O)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)
C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)
CC)C1C2CCN21)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(
C)C)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C
(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C
@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N
[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C
CSC)C(=O)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OS(O)
(O)O.OS(O)(O)O.[Zn] failed sanitization
[15:27:17] Explicit valence for atom # 2354 O, 3, is greater than permitted
Mol Br.Br.Br.Br.Br.Br.Br.Br.C.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C
@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H
]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H
](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC
1=CNC=N1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)
[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(N)=O)N
C(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C
)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@
H](CC1=CNC=N1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=
O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C
@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C
(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@
H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C
1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC
(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H
](CCC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C
)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[
C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC
(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC
C(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@
H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H
](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O
)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)
[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H
](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C
CC(=O)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(
=O)[C@@H](N)CC(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](
C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C
@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[
C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)N[C@H](
C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C
(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O
)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)
C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C
(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N
)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O
)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(
=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C
@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C
@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H]
(C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C
(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](C
CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[
C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CNC2=C1C
=CC=C2)C(=O)NCC(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@
@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@
@H](C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N1O=C(O)C[C@H]1C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](C)
C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCNC(=N)N)C(=O
)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)
N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@
H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H
](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N
[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)
N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(
=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(N)=O)C
(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(
=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@
H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N
[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](
CC1=CNC2=C1C=CC=C2)C(=O)NCC(=O)NCC(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@
@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O
)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N
)=O)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=
O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@
@H](CS)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(
=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C
CCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O
)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N
[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](C)C(=O)N[C@@H](C
O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CS)C(=O)NCC(
=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=
O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C
=CC=C2)C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]
(CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[
C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)NCC(=O)N[C@@H](CC1=CC=C
(O)C=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC
(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@H](
C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]
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H](CC3=CC=C(O)C=C3)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC(=O)[C@@H](NC(=O
)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](
CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)N
C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(
=O)[C@@H](NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC3=CC=C(O)C=C
3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H
](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CC3=CC=C(
O)C=C3)NC(=O)[C@H](CC3=CC=CC=C3)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(C)C)NC(=O)[
C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]3CCCN3C(=O)[
C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CCSC)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)[C@H](CC
CCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC3=
CC=CC=C3)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC3=CNC4=C3C=CC=C4)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]
(CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)
[C@H](CC(=O)O)NC(=O)[C@@H](N)CC(N)=O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C
@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C
)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@
H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)
C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](
C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)C(C
)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C
)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]
(C(C)C)C(=O)N2)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)C
C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@
H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](
CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[
C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(
=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C(C)C)C(=
O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N2CCC[C@H
]2C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS
)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCCN2C3=NN32)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=
O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C
@@H](C)O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(=N)N)C(=O
)N[C@@H](CCCN2NC2=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H
](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N1)C(C)C)C(C)
C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@H](C(=O)N[C@H](C
(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(
=O)NCC=O)C1CC1CN)[C@@H](C)CC)C12C3C45NC341(N)=[N+]52)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C.CN.Cl.Cl.Cl.Cl.Cl.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO
.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.O
CCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OC[C@@H]1[C@@H](O)
[C@H](O)[C@H](O)C2N[C@@H](CNC3CCCCC3)CN21.OC[C@@H]1[C@@H](O)[C@H](O)[C@H](O)C2N[C@@H](CNC3CCCCC3)CN21 failed san
itization
[15:27:20] Explicit valence for atom # 29 C, 5, is greater than permitted
Mol [H]O[C@@]([H])(N([H])[C@]1([H])[C@@]([H])([C@@]([H])(O[H])N([H])[C@@]2([H])N([H])C([H])([H])[C@]([H])(Cl)C([
H])([H])C2([H])[H])C([H])([H])[C@]([H])(Cl)C([H])([H])[C@]1([H])OC([H])([H])[H])[C@@]1([H])SC([H])([H])[C@]([H])
(C([H])([H])N(C([H])([H])[H])C2([H])([H])OC([H])([H])C([H])([H])N2[H])[C@]1([H])Cl failed sanitization
[15:27:31] Explicit valence for atom # 2037 O, 3, is greater than permitted
Mol CC1C(NC2O[C@@H](C(F)(F)F)[C@@H]3[C@@H](O)CCN23)CCC(CN)C1Cl.CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)
O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](N
C(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CCC(N)=O)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@
H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C
C(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@
@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@
@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CC
C(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C(=
O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N
[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@
H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=
O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C
C1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O
)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC1=CNC
2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C
(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(
=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(=O)O)C(=O)N[
C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=C
C=C(O)C=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)
C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=
O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CNC=
N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=
O)NCC(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC
[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)
C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)
C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC(=O
)O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C
(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)
C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N
[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](
C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCCN)C(=O)N[
C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(=N)
N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@
@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@
@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O
)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(
=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=
O)N[C@@H](CCCCN)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H
](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[
C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H]
(CCC(N)=O)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)NC
C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)
N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@]12C(=O)O1C[C@H]2O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)C(
C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)
CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C
)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O failed sanitization
[15:27:37] Explicit valence for atom # 1205 O, 3, is greater than permitted
Mol CC(O)N[C@H]1CO[C@H](CO)[C@@H](O)[C@@H]1O.CC1NC2NC([C@H](O)N3CCOCC3)CN2[C@@H](C2CCC(Cl)CC2Cl)[C@@H]1CN.CC1NC2
N[C@H]([C@H](O)N3CCOCC3)CN2[C@@H](C2CCC(Cl)CC2Cl)[C@@H]1CN.CC[C@H](C)[C@@H]1NC(=O)CNC(=O)[C@H](CC2=CNC=N2)NC(=O)
[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)
[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H
](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C
@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](C(C
)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O
)[C@H](CC2=CNC=N2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](C
C(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H](C(C
)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=C(O)C=C2)
NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H
](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCSC)N
C(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC2=CC
=C(O)C=C2)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CC=C(
O)C=C2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](C(C
)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)CNC(=O)[C@@H](NC
(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[
C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=C(O)C=C2)N
C(=O)CNC(=O)CNC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CO)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)CNC(=O)[C@H](CC2=CN
C3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=
O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H
](CO)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H
](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](C
CC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC
(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)
[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)CNC(=O)[C@H](CO)NC
(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(
=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[
C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)
NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@@H]
(NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C
@@H]2CCCN2C(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C
CCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CNC=N2)NC(=O)
[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC
2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H]
(CCC(=O)O)NC(=O)[C@H](CC(=O)N[C@@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2NC(C)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=
O)[C@@H](NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(
=O)[C@H](CO)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](
CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H
](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](
NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O
)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=
C(O)C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)CNC(=O)[C@H](CO)NC
(=O)[C@@H]2CSSC[C@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]3CCCN3C(=O)[C@H](CC(N)=O)NC(=O)[C@H
](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]3CSSC[C@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC
(=O)[C@H](CC4=CC=C(O)C=C4)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H
](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC4=CC=C(O)C=C4)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC
(=O)CNC(=O)CNC(=O)[C@@H]4CCCN4C(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC4=CC=C(O)C=C4)NC(=O)[C@H](C
CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC4=CC=C(O)C=C4)NC(=O)[C@H](CC4=CC=C(O)C=C4)
NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC4=CC=C(O)C=C4)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)
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)C)NC(=O)[C@H](CC6=CC=CC=C6)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)N[C@@H]6O[C@H](CO)[C@@H
](O)[C@H](O)[C@H]6NC(C)O)NC(=O)CNC(=O)[C@H](CC6=CC=C(O)C=C6)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CC6=CC=CC=C6)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O
)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC6=CC=C(O)C=C6)NC(=O)[C@H](CC(C)C)NC(=
O)[C@H](CC6=CC=C(O)C=C6)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC6=CNC=N6)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@
@H](NC(=O)[C@H](CC6=CNC7=C6C=CC=C7)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC6=CC=C
(O)C=C6)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC6=CC=C(O)C=
C6)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC6=CC=C(O)C=C6)NC(=O)[C@H]
(CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC6=CC=C(O)C=C6)NC(=O)[C@@H](NC(=O)[C@H](CCCCN
)NC(=O)[C@@H](N)CCCNC(=N)N)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H
](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H]
(C)O)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C
@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(C)
C)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](
C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC6
=CC=C(O)C=C6)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCN
C(=N)N)C(=O)N[C@@H](CC6=CNC7=C6C=CC=C7)C(=O)N[C@@H](CC(N)=O)C(=O)N5)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)
C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(=O)N[C@@H](CC5=CC=C(O)C=C5)C(=O)N[C@@H](CC5=CC=CC=C5)C(=O)N[C
@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C
C(=O)O)C(=O)N4)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC
)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N3)C(=O)N[C@@H](CCC(N)=O)C(=O)
N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CO)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C
@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=
O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC
CNC(=N)N)C(=O)N2)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(
C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C
)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)CSSC[C@@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CO)C(=
O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@
H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H]([C@@H]
(C)O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]
(CC2=CNC=N2)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC1=O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OCC(O)CO failed sanitization
[15:27:56] Explicit valence for atom # 5899 O, 3, is greater than permitted
Mol Br.Br.Br.Br.Br.Br.Br.Br.Br.Br.Br.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=
O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=
O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C
)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC
(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H]
(CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC
(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=
C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)N
C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]
1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC
(=O)[C@H](CCSC)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)
[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=
C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(
=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(
=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]
(CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](
NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[
C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC
(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C
@H](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(
=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=
O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@
@H](NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H]
(CCC(=O)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)
[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](CC(N)=O)NC(=O)CN)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC
)C12C3C14NC342)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@
@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@
H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N
1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C
@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=
O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)
C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C
(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H
](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O
)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C
@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[
C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@H](C(=O)N[C@H
](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H
](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@H](
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(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H]1CCC(=O)OO=C(O)CC[C@H](N)C(=O)N1)C
(C)C)[C@@H](C)CC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C
@@H](CCCCN)C(=O)O)[C@@H](C)O.Cl.Cl.Cl.Cl.Cl.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
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O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO
.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.OCCO.O
CCO.OC[C@H]1CN[C@@H](O)[C@@H](O)[C@@H]1O.OC[C@H]1CN[C@@H](O)[C@@H](O)[C@@H]1O failed sanitization
[15:28:01] Explicit valence for atom # 2041 O, 3, is greater than permitted
Mol CC(C)C[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(
=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CO)C(=O)N[C@@H](C)C(=O)O.CCCCCCCCCC(O)O.CC[C@H](C)[C@H](NC(=O)[C@H](C)NC(=O)[C@H]
(CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H
](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O
)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)N
C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)
[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCCN)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)N
C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[
C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C
@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(
N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCSC)NC(=O)
[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[
C@@H](NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC
(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)N
C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@@H]
(NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC
(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H
](NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CS)NC(=O)CNC(=
O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[
C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](N)CCCCN)C(C)C)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O
)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)
C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=
O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O
)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCC
(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@
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CC(N)=O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@
H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)
C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)
C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@
H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(
=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCC(=
O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC1=CNC=
N1)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@
H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C1=OOC(=O)[C@H](CC(C)C)N1)[C@@H](C)CC)[C
@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)
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1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](
CC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC
(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O
)[C@@H](N)CO)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N
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C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O
)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C=O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O.O.O.O.O.O.O
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.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O failed
sanitization
[15:28:18] Explicit valence for atom # 3573 O, 3, is greater than permitted
Mol CC(O)O.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC
(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)
[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](C
)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[
C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC1=C
C=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H]1CCCN1C(=
O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](
CC1=CNC=N1)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=
C2)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)
[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C
C(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[
C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)
NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C
@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC2=C1C=CC=C
2)NC(=O)CNC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O
)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O
)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC
(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)
[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H
](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)C
NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C
(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC
NC(=N)N)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O
)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)
O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@
@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(
=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CO)NC(=O)[
C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CO
)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1
CCCN1C(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(
=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C
@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=CC=C1)NC(=O)
[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)
O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@
H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)[C@@H
](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)C(C)C)[C@@H
](C)CC)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=C
C=C(O)C=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N
[C@H](C=O)CCC(=O)O)C(C)C.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](
NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)CNC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@
H](CCCCN)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(
=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CCCCN)C(C)C)C(C)C)[C@@H](C)O)[C@@H
](C)CC)C(C)C)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N
[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)
N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(O)=ONCCCC[C@H](NC(
=O)CNC(=O)[C@@H]1CC(O)=OO=C([C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC
(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C
@H](C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C
@H](CC(N)=O)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=CC=C2)NC
(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(
=O)[C@H](CCSC)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC2=C
C=C(O)C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CNC=N2)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H]
(NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@
H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[
C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H]
(CCC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[
C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)
NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)N
C(=O)[C@H](C)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)CNC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N
)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@@H](NC(=O)[C@@H
](NC(=O)[C@@H](NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCCCN)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H
](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C
@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(C)C)NC(=O)[C@@H](
NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](C
O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC
(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H
](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC2=CNC3=C2C=CC=C
3)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC(=
O)O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)
CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O)[C@@H](NC(
=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CO)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CC2=
CNC3=C2C=CC=C3)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(=O)O)NC(=
O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H
](CCC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=
O)CNC(=O)[C@H](CC2=CNC3=C2C=CC=C3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)
[C@@H]2CCCN2C(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(N)=O)C(C)
C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)
[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H]
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O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)C2NC(CCC3CCCCC3)CN21.OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H]2NC(CCC3CCCCC3)
CN12.[CaH2] failed sanitization
[15:28:21] Explicit valence for atom # 2034 C, 5, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)CNC(=O
)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)
[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)
[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=
O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC
(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C
@H](CO)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(
=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C
@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
(C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC
(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CS)NC(=O)[C@
H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)
NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H]
(CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)N
C(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)
=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C
C1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(
=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](
NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[
C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCN1NC1=N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)CN
C(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)
NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(N)=O)NC(=O)[C@H]
(CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O
)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](
CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC
(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(
=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@@H]1CCCN
1C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@
H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)
[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N
[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=
C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N
[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=
O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N
[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)
C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H
](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H]
(C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H]
(CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N
[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C
@@H](CCCCN)C(=O)N[C@H](C(=O)O)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)
C(C)C)C(C)C)[C@@H](C)O.CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=
CNC=N1)NC(=O)CNC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](
NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H
](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O
)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)
C)NC(=O)[C@H](CS)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@
H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)
[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)N
C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)
[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC
NC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O
)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(
C)C)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C
(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC
=C1)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[
C@H](CC(C)C)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O
)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O
)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CO)NC(=O)[C@H](C
S)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=C(O
)C=C1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)N
C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H
](CCC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C
@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](
CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](
CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(
=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCN
C(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=
O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C
1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)N)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)
C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)
C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)
C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=
C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)
C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H]
(CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)
C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCN1N=C1N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=C
C=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)
N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N
[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N
[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)
C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(
=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)NCC(=O)N[C@H]1CC(C)C2OC21=O)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@
@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O.NC1NCNC2C1NCN2[C@@H]1O[C@H](CSCC[C@H](N)C(O)O)[C@@H](O)[C
@H]1O.NC1NCNC2C1NCN2[C@@H]1O[C@H](CSCC[C@H](N)C(O)O)[C@@H](O)[C@H]1O.NS(O)(O)C1CC[C@@H]2CCNC[C@H]2C1.NS(O)(O)C1C
C[C@@H]2CCNC[C@H]2C1.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O failed sanitization
[15:28:33] Explicit valence for atom # 2206 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C
@H](CCSC)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O
)[C@H](C)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)
[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1
)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@@H
](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=CC=C1)NC(=O)
[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](C)NC(=O)[C@@H](N=C(O)[C@H](CC1
CCC(O[PH](O)(O)O)CC1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O
)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)
=O)NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC
CNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C
C1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)
NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=
O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H
](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=
O)[C@H](CS)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H
](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@
@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)
[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H
](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C
CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](
CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H
](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=
O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H]
(CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[
C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C
CCCN)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[
C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)[C
@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H]
(NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=
O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)O
)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H]
(C)CC)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)[C
@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]
(CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(=O)O)C(=
O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](
CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1C
CC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(
=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](
CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1
=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N)
N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=
O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N
[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(
=O)N[C@@H](CO)C(=O)N[C@H](C1=O[C@@](CO)(C2=OO2)N1)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C.CC[C@H](C)[C@H]
(NC(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CCSC)NC(=O)CNC(
=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=C
C=C2)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@H
](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](
CO)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=
O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC1=C
NC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCCCN)NC(=O)[
C@H](C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](C)NC(=O)[C@@H](N=C(O)[C@H](CC1CCC(O[PH](O)(O)O)CC
1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)
N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@
H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(
=O)O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H
](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@
@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(=O)O)NC(=O)
[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=
O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC1=CC=C(O)
C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@
@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@
H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CCS
C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=C(O)C=
C1)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@@H]1CCCN1C(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)
[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H
](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](
NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC
(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC
(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@
H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](
NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC
1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](C
CC(=O)O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C
@H](CCCCN)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)
O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1
=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(=O)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)
O)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)[C@@H
](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)O)[
C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H
](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(=O)O)C(
=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]
(CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1
CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CS)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCCN)C
(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]
(CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC
1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCNC(=N
)N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(
=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(=O)O)C(=O)
N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C
(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@]12O=C13O1C2O13)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C.CO[C@H](C1CCC
CC1)C(O)N1CC2NNC(NC(O)C3CCC(N4CCN(C)CC4)CC3)C2C1.CO[C@H](C1CCCCC1)C(O)N1CC2NNC(NC(O)C3CCC(N4CCN(C)CC4)CC3)C2C1.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.[MgH2
].[MgH2] failed sanitization
[15:28:45] Explicit valence for atom # 21 C, 5, is greater than permitted
Mol [H]ON([H])C1([H])([H])N([H])[C@@]([H])(C([H])([H])O[H])[C@]([H])(O[C@]2([H])O[C@]([H])(C([H])([H])O[H])[C@@]
([H])(O[C@]3([H])O[C@@]([H])(C([H])([H])O[H])[C@]([H])(OC([H])([H])[H])[C@@]([H])(O[H])[C@]3([H])O[H])[C@]([H])(
O[H])[C@]2([H])O[H])[C@@]([H])(O[H])[C@@]1([H])O[H] failed sanitization
[15:28:52] Explicit valence for atom # 4107 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)CNC(=O
)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)
[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)
[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=
O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC
(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C
@H](CO)NC(=O)CNC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(
=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C
@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H]
(C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC
(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H]1CSSC[C@H](N
C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H
](C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)
C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](C)NC(=O)[C
@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@@H]2CCCN2C(=O
)[C@H](C)NC(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C
(C)C)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](
CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O
)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=
O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC
)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H]([C@@H]
(C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C
)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC2=CC=CC
=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCS
C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O
)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C
(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@
H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC2=C
C=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC2=
CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[
C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCC(=O
)O)C(=O)N[C@H](C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCCCN)C(=
O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=
O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@
@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CCC
(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=
O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(C)C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C
(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](C
C2=CC=CC=C2)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CO
)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=CC=
C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(=O)O)C(=O)N[
C@@H](CC2=CNC=N2)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(
=N)N)C(=O)N2CCC[C@H]2C(=O)NCC(=O)NCC(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](
CC(C)C)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[
C@@H](CO)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)NC
C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[
C@H](C(=O)N2CCC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O
)O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O
)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@
@H](CCCNC(=N)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=
C(O)C=C2)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N2CCC[C@H]2C(=O)N[C@@H](C)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC(C)
C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=
O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@
H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@]23C(=O)O2C3(C)C)C(C)C)C
(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O)[C@@H](C)CC)[C@@H](C
)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)CSSC[C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(
=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]2CCCN2C(=O)[C@H](C)NC(=O)[C@H](CC2=CC=C(O)C=C2)N
C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(
=O)[C@H](C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC2=CC=CC=C2)NC(=O)[C@H](CCC
NC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@@H]
(NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O)C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CC(
N)=O)C(=O)NCC(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CCCCN)C(=O)N[
C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(
=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(=
O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)
C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N2CC
C[C@H]2C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H
](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC
=N2)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([
C@@H](C)O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](
CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)
=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O
)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N2CCC[C@H]2C(=O)NCC(=O)N[
C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H](CO)C(=O)N[C@
@H](CCSC)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H]
(C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(=O)O)C(=O)NCC(=O)N[C@@H](CCCCN)
C(=O)NCC(=O)N[C@@H](CCC(=O)O)C(=O)N1)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O
)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@
@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CCC(=
O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N1CCC[C@
H]1C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=
O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)
N)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=
O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@H](C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@
H](C(=O)N[C@@H](CCSC)C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC
(N)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(
=O)NCC(=O)N[C@H](C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C)C(=O)N[C@@H](CC1=CNC2=C1C=CC
=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)O)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)
O)[C@@H](C)CC)[C@@H](C)O)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)C(C)C)[C@@H](C)O.C[S@@H](CC[C@H](N)C(O)O)C[C@H]1O[C@@H](N
2CNC3C(N)NCNC32)[C@H](O)[C@@H]1O.C[S@@H](CC[C@H](N)C(O)O)C[C@H]1O[C@@H](N2CNC3C(N)NCNC32)[C@H](O)[C@@H]1O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OC[C@H]1CC2CCC(N(O)O)CC2CN1.OC[C@H]1CC2CC[C@@H](N(O)O)CC2CN1.OC[C@H]
1C[C@H]2CC[C@@H](N(O)O)CC2CN1.O[PH](O)(O)O failed sanitization
[15:29:06] Explicit valence for atom # 1 C, 5, is greater than permitted
Mol [H]ON([H])C([H])([H])(N([H])[H])N([H])C([H])([H])C([H])([H])[C@@]([H])(C([H])(O[H])O[H])[N+]([H])([H])[H] fa
iled sanitization
[15:29:09] Explicit valence for atom # 391 O, 4, is greater than permitted
Mol CC[C@@H]1C[C@]1(N[C@@H](O)[C@@H]1C[C@@H]2CN1[C@@H](O)[C@H](C(C)(C)C)NC(O)OCC(C)(C)CCCC[C@@H]1CCCC3CN(CC31)C(
O)O2)C(O)NS(O)(O)C1CC1.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)CNC(=O)[C@
H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)CNC(=O)
[C@H](C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC
(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H
](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CCCN
C(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](NC(
=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@
H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O
)CNC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(
=O)[C@@H]1CCCN2C3(=N)NO23C(=O)CC[C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](
CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC
(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CCC(=O)O)N
C(=O)[C@H](CCC(=O)O)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[
C@H](C)NC(=O)[C@H](CC2=CC=C(O)C=C2)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C
@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]
(NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O
)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC2=CNC=N2)NC(=O)[C@H](CO)NC(=O)CN)C(C)C)C(C)C)[C@@H](C)CC)
C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=
O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@
@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]
(C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C(C
)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C
C2=CC=C(O)C=C2)C(=O)N[C@@H](CC2=CNC=N2)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(=
N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@@H]
(CCCCN)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC
)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O
)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CC2=CNC3=C
2C=CC=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)
N1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CC1=CC=CC=C1)C(
=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCC1N2C
(=N)N12)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=
O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H
](CC(C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC12NC1(=N)N2)C1=OO1)[C@@
H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OS(O)(O)O.OS(O)(O)O.[Zn] failed sanitization
[15:29:42] Explicit valence for atom # 164 O, 3, is greater than permitted
Mol CC[C@@H]1C[C@]1(NC(O)[C@@H]1C[C@@H]2CN1[C@@H](O)[C@H](C(C)(C)C)N[C@H](O)OCC(C)(C)CCCC[C@H]1CCCC3CN(CC31)C(O)
O2)[C@@H](O)NS(O)(O)C1CC1.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)CNC(=O)
[C@H](C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)CNC(
=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO
)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)CNC(=O)[C@H](C
CCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](
NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)
[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC
(=O)CNC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)
NC(=O)[C@@H]1CCCNC2(=NN2)OC(=O)CC[C@H](NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]
(CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H]2CCC(N)=OO
=C([C@H](CCC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CS)NC(=O)CNC(=O)[C@H](CC3OC3=O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H
](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC3=CC=C(O)C=C3)NC
(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]3CC(O)=ON3C(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O
)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)C
NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](C)NC(=O)[C@H](
CCSC)NC(=O)[C@H](CC3=CNC=N3)NC(=O)[C@@H](N)CO)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C3
C4C(O)=O43)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N2)[C@@H](C)O)C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)
C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C)C(=O)N[C@@H](
[C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@
@H](C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](
C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H
](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC2=CNC=N2)C(=O)NCC(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCN
C(=N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N2CCC[C@H]2C(=O)N[C@
@H](CCC2CN2)C(=O)NCC(=O)N2CCC[C@H]2C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]
(CCSC)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](
CC(=O)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CC2=C
NC3=C2C=CC=C3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N2CCC[C@H]2C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CO)
C(=O)N1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CC1=CC=CC=
C1)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CC
CNC(=N)N)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)N[C
@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(
C)C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CO)C1=O
O1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OS(O)(O)O.OS(O)(
O)O.OS(O)(O)O.OS(O)(O)O.[Zn] failed sanitization
[15:30:26] Explicit valence for atom # 1064 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](
NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)
[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@
H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)
[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](
NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[
C@H](C)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)
NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC
(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O
)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](
CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C
)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O
)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(
C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](
CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC
(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CN)[C@@H](C
)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)C
C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@
H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC
(=N)N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC
=N1)C1=OO1.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)
[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1
)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC
(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H]
(NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)
[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)
NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[
C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC
(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H]
(CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O
)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]
(CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C
O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C
@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O
)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC
(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(
=O)[C@@H](N)CC1=CC=C(O)C=C1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C
@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(=
O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(
=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N
[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC=N1)C1=OO1.CC[C@H](C)[C@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(
=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H
](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC
CNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](C
)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=
O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](C)NC(=O)[C@H](CO)NC(=
O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C
CCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC=N1)NC(=O
)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O
)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=
O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC
(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](
CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@@H](NC(=
O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](C)NC(=
O)[C@H](C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O
)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[
C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](N)C(C)C)[C@@H](C)O)[C@@H](C)O)C(C)C)[C
@@H](C)CC)C(C)C)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)[C@@H](C)CC)C(
C)C)[C@@H](C)CC)[C@@H](C)O)C(C)C)[C@@H](C)CC)C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=
O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC1
=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CC1=CNC=N1)C(=O)O.CC[C@H](C)[
C@H](NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)CNC(=O)[C@@H](NC(=O)[C@H](C)N
C(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CO)NC(=O)
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.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O
.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.OC(O)[C@@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC
(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]
1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[
C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O
)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](
O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC
(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]
1(O)CC[C@@H](O)[C@H](O)C1.OC(O)[C@]1(O)CC[C@@H](O)[C@H](O)C1.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)
CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.OCC(O)CO.O[C@@H]1C[C@@]23O[C@@]2(C[C@H]1O)C3(O)O failed sanitiza
tion
[15:30:34] Explicit valence for atom # 3443 O, 3, is greater than permitted
Mol CC1C[C@H]2C(C)C([C@@H]3C[C@H](C)C(O)O3)CC[C@@]23CCCNC3CCCC(C)[C@@H]2O[C@@H](CC[C@@H]1O)C[C@H]2C.CC1C[C@H]2C(
C)C([C@@H]3C[C@H](C)C(O)O3)CC[C@@]23CCCNC3CCCC(C)[C@@H]2O[C@@H](CC[C@@H]1O)C[C@H]2C.CC1C[C@H]2C(C)C([C@@H]3C[C@H
](C)C(O)O3)CC[C@@]23CCCNC3CCCC(C)[C@@H]2O[C@@H](CC[C@@H]1O)C[C@H]2C.CC1C[C@H]2C(C)C([C@@H]3C[C@H](C)C(O)O3)CC[C@
@]23CCCNC3CCCC(C)[C@@H]2O[C@@H](CC[C@@H]1O)C[C@H]2C.CC1C[C@H]2C(C)C([C@@H]3C[C@H](C)C(O)O3)CC[C@@]23CCCN[C@@H]3C
CCC(C)[C@@H]2O[C@@H](CC[C@@H]1O)C[C@H]2C.CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC
(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN1NC1=N)NC(=O)[C
@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@
H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[
C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(
=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O
)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCSC)NC(=O)[C@H](
CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC
(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)
NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)
O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C
CCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C
@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H
]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H
]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)
[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)N
C(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)N
C(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O
)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](N)CC(=O)O)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](
C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)C
C)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C
(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C
(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)
C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@H]1CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN
)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@H](C(=O)N[C@@H](CC2=C
C=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O
)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O
)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@
@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC
CN)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@
H](C)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=
O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N[C@H]2CSSC[C@@H](C
(=O)N3CCC[C@H]3C(=O)N[C@@H](CCC(=O)O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](C(=O)N[C@@H](CC(=O
)O)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](
CC3=CC=CC=C3)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCCNC(=N)N)C(=O)
N[C@]34CO3C4=O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)NC2=O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@
H](C)O)[C@@H](C)CC)C(C)C)C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(
=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CCCN2C(=O)[
C@H](CC(=O)O)NC1=O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C.CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CC
CN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](
CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(
=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C
@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC
=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[
C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H
](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC
1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@
H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](
NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C
@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC
(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]
(CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCC
N1C(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H
](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)
NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N
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C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C
@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N[C@H]2CSSC[C@@H](C(=O)N3CCC[C@H]3C(=O)N[C@@H](CCC(=O)O)C(=O)N3CCC[C@H
]3C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC
(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](C
CC(=O)O)C(=O)N[C@]3(CCCNC(=N)N)OC3=O)C(C)C)C(C)C)C(C)C)[C@@H](C)CC)NC2=O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC
)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC
(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC
(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC1=O)[C@@H](C)CC)C(C)C)[C@@H](C)O)C(C)C)C(C)C.CC[C@H](C)[C@H](NC(=O)[C@H](CC
C(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[
C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C
@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2
)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N
)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](C
C1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC
2=C1C=CC=C2)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H
](CCCCN)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C
@H](CCC(=O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H]
(CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)
[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O
)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC
(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[
C@@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(
=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C
C(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC1=CNC=N1)NC(=O)[C@H](C
C(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C
@H](CCCCN)NC(=O)[C@@H](N)CC1=CC=C(O)C=C1)[C@@H](C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@
@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C
(C)C)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(=O)O)C(=O)
NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@
H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1
)C(=O)N[C@@H](CCSC)C(=O)N[C@H]1CSSC[C@@H](C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=CC=C
2)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CNC3=C2C=CC=C3)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](C
O)C(=O)NCC(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(
=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[
C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)
N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=C(
O)C=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C
@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N
[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)N[C@H]2CSSC[C@@H](C(=O)N3CCC[C@H]3C(=O)N[C@@
H](CCC(=O)O)C(=O)N3CCC[C@H]3C(=O)N[C@@H](CC3=CC=C(O)C=C3)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@
H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)N[C@@H]
(CCCNC(=N)N)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@@H](CCCNC(=N)N)C(=O)N[C@]3(CCCNC(=N)N)OC3=O)C(C)C)C(C)C)C(C)C)[C@@H](
C)CC)NC2=O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)NC(=O)[C@
H]([C@@H](C)O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)
NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(=O)O)NC1=O)[C@@H](C)CC)C(C)C)[C@
@H](C)O)C(C)C)C(C)C.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.O.
O.O.O.O.O.O.O.O.O.O failed sanitization
[15:30:40] Explicit valence for atom # 1686 O, 3, is greater than permitted
Mol CC[C@H](C)[C@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[
C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCC(=
O)O)NC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H]1CCCN1C(
=O)[C@@H](NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H
](CO)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@@H](
NC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)[C@H](CC1=CC=C(O)C=C1)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H]1CCC
N1C(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@
H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H
](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC1=CNC2=C1C=CC=C2)NC(=O)[C@H](CC1=CC=C(O)C=C1)
NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCC(=O)O)NC(=O)[C@H](CC(N)=O)NC(=O)
[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC(=O)O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H
](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CC1=CC=CC=C1)NC(=O)CNC(=O
)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CC(=O)O)NC(
=O)[C@H](CC(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](NC(=O)[C@@H]1CCCN1C(=O)CNC(=O)[C@@H]1CCCN1C(=O)[C@H](CC1=CC=C(O)
C=C1)NC(=O)[C@H](CCSC)NC(=O)[C@@H]1CCCN1C(=O)[C@H](CO)NC(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC1
=CC=CC=C1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]
(CCCNC(=N)N)NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CCC(N)=O)[C@@H]
(C)O)[C@@H](C)O)C(C)C)[C@@H](C)O)[C@@H](C)O)[C@@H](C)CC)C(C)C)C(C)C)[C@@H](C)O)C(C)C)C(C)C)[C@@H](C)CC)[C@@H](C)
O)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)O)C(C)C)C(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C(=
O)N[C@H](C(=O)N[C@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CC(=O)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@@H
](CCSC)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@H](C(=O)N1CCC[C@H]1C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C
CCNC(=N)N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](CCSC)C(=O)N[C@H]1CSSC[C@@H]
(C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC
2=CNC3=C2C=CC=C3)C(=O)N[C@H](C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC2=CC=CC=C2)C(=O)
N[C@@H](CCC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N[C@@H
](CC(=O)O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](C
C(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](C)C
(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC2=CC=C(O)C=C2)C(=O)N[C@@H](CCC(=O)O)C(=O)N[C@H]
(C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](C
CCNC(=N)N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC2=CNC=N2)C(=O)N[C@@H](CC2=CC=C(
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)(O)O.O[PH](O)(O)O failed sanitization
[15:30:46] Explicit valence for atom # 3393 O, 3, is greater than permitted
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nitization

Let's now train a simple random forest model on this dataset.

seed = 42 # Set a random seed to get stable results

sklearn_model = RandomForestRegressor(n_estimators=100, max_features='sqrt')
sklearn_model.random_state = seed
model = dc.models.SklearnModel(sklearn_model)
model.fit(train_dataset)

Let's see what our accuracies looks like!

metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)

evaluator = Evaluator(model, train_dataset, [])

train_r2score = evaluator.compute_model_performance([metric])
print("RF Train set R^2 %f" % (train_r2score["pearson_r2_score"]))

evaluator = Evaluator(model, test_dataset, [])

test_r2score = evaluator.compute_model_performance([metric])
print("RF Test set R^2 %f" % (test_r2score["pearson_r2_score"]))

RF Train set R^2 0.536155

RF Test set R^2 0.000014

Ok, it looks like we have lower accuracy than the ligand-only dataset. Nonetheless, it's probably still useful to have a
protein-ligand model since it's likely to learn different features than the the pure ligand-only model.

Further reading
So far we have used DeepChem's docking module with the AutoDock Vina backend to generate docking scores for the
PDBbind dataset. We trained a simple machine learning model to directly predict binding affinities, based on featurizing
the protein-ligand complexes. We might want to try more sophisticated docking protocols, like the deep learning
framework gnina. You can read more about using convolutional neural nets for protein-ligand scoring here. And here is a
review of machine learning-based scoring functions.

Congratulations! Time to join the Community!

Congratulations on completing this tutorial notebook! If you enjoyed working through the tutorial, and want to continue
working with DeepChem, we encourage you to finish the rest of the tutorials in this series. You can also help the
DeepChem community in the following ways:
Star DeepChem on GitHub
This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Modeling Protein-Ligand Interactions with Atomic
Convolutions
By Nathan C. Frey | Twitter and Bharath Ramsundar | Twitter

This DeepChem tutorial introduces the Atomic Convolutional Neural Network. We'll see the structure of the
AtomicConvModel and write a simple program to run Atomic Convolutions.

ACNN Architecture
ACNN’s directly exploit the local three-dimensional structure of molecules to hierarchically learn more complex chemical
features by optimizing both the model and featurization simultaneously in an end-to-end fashion.

The atom type convolution makes use of a neighbor-listed distance matrix to extract features encoding local chemical
environments from an input representation (Cartesian atomic coordinates) that does not necessarily contain spatial
locality. The following methods are used to build the ACNN architecture:

Distance Matrix
The distance matrix

is constructed from the Cartesian atomic coordinates

. It calculates distances from the distance tensor

. The distance matrix construction accepts as input a

coordinate matrix

. This matrix is “neighbor listed” into a

matrix

R = tf.reduce_sum(tf.multiply(D, D), 3) # D: Distance Tensor

R = tf.sqrt(R) # R: Distance Matrix
return R

Atom type convolution

The output of the atom type convolution is constructed from the distance matrix

and atomic number matrix

. The matrix

is fed into a (1x1) filter with stride 1 and depth of

, where

is the number of unique atomic numbers (atom types) present in the molecular system. The atom type convolution
kernel is a step function that operates on the neighbor distance matrix

Radial Pooling layer

Radial Pooling is basically a dimensionality reduction process that down-samples the output of the atom type
convolutions. The reduction process prevents overfitting by providing an abstracted form of representation through
feature binning, as well as reducing the number of parameters learned. Mathematically, radial pooling layers pool
over tensor slices (receptive fields) of size (1x

x1) with stride 1 and a depth of

, where

is the number of desired radial filters and

is the maximum number of neighbors.

Atomistic fully connected network

Atomic Convolution layers are stacked by feeding the flattened (
,

) output of the radial pooling layer into the atom type convolution operation. Finally, we feed the tensor row-wise
(per-atom) into a fully-connected network. The same fully connected weights and biases are used for each atom in a
given molecule.

Now that we have seen the structural overview of ACNNs, we'll try to get deeper into the model and see how we can
train it and what we expect as the output.

For the training, we will use the publicly available PDBbind dataset. In this example, every row reflects a protein-ligand
complex and the target is the binding affinity (

) of the ligand to the protein in the complex.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!pip install -q condacolab

import condacolab
condacolab.install()
!/usr/local/bin/conda info -e

!/usr/local/bin/conda install -c conda-forge pycosat mdtraj pdbfixer openmm -y -q # needed for AtomicConvs

!pip install --pre deepchem

import deepchem
deepchem.__version__

import deepchem as dc
import os

import numpy as np
import tensorflow as tf

import matplotlib.pyplot as plt

from rdkit import Chem

from deepchem.molnet import load_pdbbind

from deepchem.models import AtomicConvModel
from deepchem.feat import AtomicConvFeaturizer

Getting protein-ligand data

If you worked through Tutorial 13 on modeling protein-ligand interactions, you'll already be familiar with how to obtain a
set of data from PDBbind for training our model. Since we explored molecular complexes in detail in the previous
tutorial), this time we'll simply initialize an AtomicConvFeaturizer and load the PDBbind dataset directly using
MolNet.

f1_num_atoms = 100 # maximum number of atoms to consider in the ligand

f2_num_atoms = 1000 # maximum number of atoms to consider in the protein
max_num_neighbors = 12 # maximum number of spatial neighbors for an atom

acf = AtomicConvFeaturizer(frag1_num_atoms=f1_num_atoms,
frag2_num_atoms=f2_num_atoms,
complex_num_atoms=f1_num_atoms+f2_num_atoms,
max_num_neighbors=max_num_neighbors,
neighbor_cutoff=4)

load_pdbbind allows us to specify if we want to use the entire protein or only the binding pocket ( pocket=True ) for
featurization. Using only the pocket saves memory and speeds up the featurization. We can also use the "core" dataset
of ~200 high-quality complexes for rapidly testing our model, or the larger "refined" set of nearly 5000 complexes for
more datapoints and more robust training/validation. On Colab, it takes only a minute to featurize the core PDBbind set!
This is pretty incredible, and it means you can quickly experiment with different featurizations and model architectures.

%%time
tasks, datasets, transformers = load_pdbbind(featurizer=acf,
save_dir='.',
data_dir='.',
pocket=True,
reload=False,
set_name='core')

/usr/local/lib/python3.7/dist-packages/numpy/core/_asarray.py:83: VisibleDeprecationWarning: Creating an ndarray

Unfortunately, if you try to use the "refined" dataset, there are some complexes that cannot be featurized. To resolve
this issue, rather than increasing complex_num_atoms , simply omit the lines of the dataset that have an x value of
None

class MyTransformer(dc.trans.Transformer):
def transform_array(x, y, w, ids):
kept_rows = x != None
return x[kept_rows], y[kept_rows], w[kept_rows], ids[kept_rows],

datasets = [d.transform(MyTransformer) for d in datasets]

datasets

(<DiskDataset X.shape: (154, 9), y.shape: (154,), w.shape: (154,), ids: ['1mq6' '3pe2' '2wtv' ... '3f3c' '4gqq'
'2x00'], task_names: [0]>,
<DiskDataset X.shape: (19, 9), y.shape: (19,), w.shape: (19,), ids: ['3ivg' '4de1' '4tmn' ... '2vw5' '1w3l' '2
zjw'], task_names: [0]>,
<DiskDataset X.shape: (20, 9), y.shape: (20,), w.shape: (20,), ids: ['1kel' '2w66' '2xnb' ... '2qbp' '3lka' '1
qi0'], task_names: [0]>)

train, val, test = datasets

Training the model

Now that we've got our dataset, let's go ahead and initialize an AtomicConvModel to train. Keep the input parameters
the same as those used in AtomicConvFeaturizer , or else we'll get errors. layer_sizes controls the number of
layers and the size of each dense layer in the network. We choose these hyperparameters to be the same as those used
in the original paper.

acm = AtomicConvModel(n_tasks=1,
frag1_num_atoms=f1_num_atoms,
frag2_num_atoms=f2_num_atoms,
complex_num_atoms=f1_num_atoms+f2_num_atoms,
max_num_neighbors=max_num_neighbors,
batch_size=12,
layer_sizes=[32, 32, 16],
learning_rate=0.003,
)

losses, val_losses = [], []

%%time
max_epochs = 50

metric = dc.metrics.Metric(dc.metrics.score_function.rms_score)
step_cutoff = len(train)//12
def val_cb(model, step):
if step%step_cutoff!=0:
return
val_losses.append(model.evaluate(val, metrics=[metric])['rms_score']**2) # L2 Loss
losses.append(model.evaluate(train, metrics=[metric])['rms_score']**2) # L2 Loss

acm.fit(train, nb_epoch=max_epochs, max_checkpoints_to_keep=1,

callbacks=[val_cb])

CPU times: user 2min 41s, sys: 11.4 s, total: 2min 53s
Wall time: 2min 47s

The loss curves are not exactly smooth, which is unsurprising because we are using 154 training and 19 validation
datapoints. Increasing the dataset size may help with this, but will also require greater computational resources.

f, ax = plt.subplots()
ax.scatter(range(len(losses)), losses, label='train loss')
ax.scatter(range(len(val_losses)), val_losses, label='val loss')
plt.legend(loc='upper right');

The ACNN paper showed a Pearson

score of 0.912 and 0.448 for a random 80/20 split of the PDBbind core train/test sets. Here, we've used an 80/10/10
training/validation/test split and achieved similar performance for the training set (0.943). We can see from the
performance on the training, validation, and test sets (and from the results in the paper) that the ACNN can learn
chemical interactions from small training datasets, but struggles to generalize. Still, it is pretty amazing that we can
train an AtomicConvModel with only a few lines of code and start predicting binding affinities!
From here, you can experiment with different hyperparameters, more challenging splits, and the "refined" set of
PDBbind to see if you can reduce overfitting and come up with a more robust model.

score = dc.metrics.Metric(dc.metrics.score_function.pearson_r2_score)
for tvt, ds in zip(['train', 'val', 'test'], datasets):
print(tvt, acm.evaluate(ds, metrics=[score]))

train {'pearson_r2_score': 0.9311347622675604

val {'pearson_r2_score': 0.5162870575992874}
test {'pearson_r2_score': 0.4756633065901693}

Further reading
We have explored the ACNN architecture and used the PDBbind dataset to train an ACNN to predict protein-ligand
binding energies. For more information, read the original paper that introduced ACNNs: Gomes, Joseph, et al. "Atomic
convolutional networks for predicting protein-ligand binding affinity." arXiv preprint arXiv:1703.10603 (2017). There are
many other methods and papers on predicting binding affinities. Here are a few interesting ones to check out:
predictions using only ligands or proteins, molecular docking with deep learning, and AtomNet.

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Conditional Generative Adversarial Network
A Generative Adversarial Network (GAN) is a type of generative model. It consists of two parts called the "generator"
and the "discriminator". The generator takes random values as input and transforms them into an output that
(hopefully) resembles the training data. The discriminator takes a set of samples as input and tries to distinguish the
real training samples from the ones created by the generator. Both of them are trained together. The discriminator tries
to get better and better at telling real from false data, while the generator tries to get better and better at fooling the
discriminator.

A Conditional GAN (CGAN) allows additional inputs to the generator and discriminator that their output is conditioned on.
For example, this might be a class label, and the GAN tries to learn how the data distribution varies between classes.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands.

!pip install --pre deepchem

import deepchem
deepchem.__version__

For this example, we will create a data distribution consisting of a set of ellipses in 2D, each with a random position,
shape, and orientation. Each class corresponds to a different ellipse. Let's randomly generate the ellipses. For each one
we select a random center position, X and Y size, and rotation angle. We then create a transformation matrix that maps
the unit circle to the ellipse.

import deepchem as dc
import numpy as np
import tensorflow as tf

n_classes = 4
class_centers = np.random.uniform(-4, 4, (n_classes, 2))
class_transforms = []
for i in range(n_classes):
xscale = np.random.uniform(0.5, 2)
yscale = np.random.uniform(0.5, 2)
angle = np.random.uniform(0, np.pi)
m = [[xscale*np.cos(angle), -yscale*np.sin(angle)],
[xscale*np.sin(angle), yscale*np.cos(angle)]]
class_transforms.append(m)
class_transforms = np.array(class_transforms)

This function generates random data from the distribution. For each point it chooses a random class, then a random
position in that class' ellipse.

def generate_data(n_points):
classes = np.random.randint(n_classes, size=n_points)
r = np.random.random(n_points)
angle = 2*np.pi*np.random.random(n_points)
points = (r*np.array([np.cos(angle), np.sin(angle)])).T
points = np.einsum('ijk,ik->ij', class_transforms[classes], points)
points += class_centers[classes]
return classes, points

Let's plot a bunch of random points drawn from this distribution to see what it looks like. Points are colored based on
their class label.

%matplotlib inline
import matplotlib.pyplot as plot
classes, points = generate_data(1000)
plot.scatter(x=points[:,0], y=points[:,1], c=classes)

<matplotlib.collections.PathCollection at 0x1584692d0>
Now let's create the model for our CGAN. DeepChem's GAN class makes this very easy. We just subclass it and
implement a few methods. The two most important are:

create_generator() constructs a model implementing the generator. The model takes as input a batch of random
noise plus any condition variables (in our case, the one-hot encoded class of each sample). Its output is a synthetic
sample that is supposed to resemble the training data.

create_discriminator() constructs a model implementing the discriminator. The model takes as input the
samples to evaluate (which might be either real training data or synthetic samples created by the generator) and
the condition variables. Its output is a single number for each sample, which will be interpreted as the probability
that the sample is real training data.

In this case, we use very simple models. They just concatenate the inputs together and pass them through a few dense
layers. Notice that the final layer of the discriminator uses a sigmoid activation. This ensures it produces an output
between 0 and 1 that can be interpreted as a probability.

We also need to implement a few methods that define the shapes of the various inputs. We specify that the random
noise provided to the generator should consist of ten numbers for each sample; that each data sample consists of two
numbers (the X and Y coordinates of a point in 2D); and that the conditional input consists of n_classes numbers for
each sample (the one-hot encoded class index).

from tensorflow.keras.layers import Concatenate, Dense, Input

class ExampleGAN(dc.models.GAN):

def get_noise_input_shape(self):
return (10,)

def get_data_input_shapes(self):
return [(2,)]

def get_conditional_input_shapes(self):
return [(n_classes,)]

def create_generator(self):
noise_in = Input(shape=(10,))
conditional_in = Input(shape=(n_classes,))
gen_in = Concatenate()([noise_in, conditional_in])
gen_dense1 = Dense(30, activation=tf.nn.relu)(gen_in)
gen_dense2 = Dense(30, activation=tf.nn.relu)(gen_dense1)
generator_points = Dense(2)(gen_dense2)
return tf.keras.Model(inputs=[noise_in, conditional_in], outputs=[generator_points])

def create_discriminator(self):
data_in = Input(shape=(2,))
conditional_in = Input(shape=(n_classes,))
discrim_in = Concatenate()([data_in, conditional_in])
discrim_dense1 = Dense(30, activation=tf.nn.relu)(discrim_in)
discrim_dense2 = Dense(30, activation=tf.nn.relu)(discrim_dense1)
discrim_prob = Dense(1, activation=tf.sigmoid)(discrim_dense2)
return tf.keras.Model(inputs=[data_in, conditional_in], outputs=[discrim_prob])

gan = ExampleGAN(learning_rate=1e-4)

Now to fit the model. We do this by calling fit_gan() . The argument is an iterator that produces batches of training
data. More specifically, it needs to produce dicts that map all data inputs and conditional inputs to the values to use for
them. In our case we can easily create as much random data as we need, so we define a generator that calls the
generate_data() function defined above for each new batch.

def iterbatches(batches):
for i in range(batches):
classes, points = generate_data(gan.batch_size)
classes = dc.metrics.to_one_hot(classes, n_classes)
yield {gan.data_inputs[0]: points, gan.conditional_inputs[0]: classes}

gan.fit_gan(iterbatches(5000))

Ending global_step 999: generator average loss 0.87121, discriminator average loss 1.08472
Ending global_step 1999: generator average loss 0.968357, discriminator average loss 1.17393
Ending global_step 2999: generator average loss 0.710444, discriminator average loss 1.37858
Ending global_step 3999: generator average loss 0.699195, discriminator average loss 1.38131
Ending global_step 4999: generator average loss 0.694203, discriminator average loss 1.3871
TIMING: model fitting took 31.352 s

Have the trained model generate some data, and see how well it matches the training distribution we plotted before.

classes, points = generate_data(1000)

one_hot_classes = dc.metrics.to_one_hot(classes, n_classes)
gen_points = gan.predict_gan_generator(conditional_inputs=[one_hot_classes])
plot.scatter(x=gen_points[:,0], y=gen_points[:,1], c=classes)

<matplotlib.collections.PathCollection at 0x160dedf50>

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Training a Generative Adversarial Network on MNIST
In this tutorial, we will train a Generative Adversarial Network (GAN) on the MNIST dataset. This is a large collection of
28x28 pixel images of handwritten digits. We will try to train a network to produce new images of handwritten digits.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

To begin, let's import all the libraries we'll need and load the dataset (which comes bundled with Tensorflow).

import deepchem as dc
import tensorflow as tf
from deepchem.models.optimizers import ExponentialDecay
from tensorflow.keras.layers import Conv2D, Conv2DTranspose, Dense, Reshape
import matplotlib.pyplot as plot
import matplotlib.gridspec as gridspec
%matplotlib inline

mnist = tf.keras.datasets.mnist.load_data(path='mnist.npz')
images = mnist[0][0].reshape((-1, 28, 28, 1))/255
dataset = dc.data.NumpyDataset(images)

Let's view some of the images to get an idea of what they look like.

def plot_digits(im):
plot.figure(figsize=(3, 3))
grid = gridspec.GridSpec(4, 4, wspace=0.05, hspace=0.05)
for i, g in enumerate(grid):
ax = plot.subplot(g)
ax.set_xticks([])
ax.set_yticks([])
ax.imshow(im[i,:,:,0], cmap='gray')

plot_digits(images)

Now we can create our GAN. Like in the last tutorial, it consists of two parts:

1. The generator takes random noise as its input and produces output that will hopefully resemble the training data.
2. The discriminator takes a set of samples as input (possibly training data, possibly created by the generator), and
tries to determine which are which.

This time we will use a different style of GAN called a Wasserstein GAN (or WGAN for short). In many cases, they are
found to produce better results than conventional GANs. The main difference between the two is in the discriminator
(often called a "critic" in this context). Instead of outputting the probability of a sample being real training data, it tries
to learn how to measure the distance between the training distribution and generated distribution. That measure can
then be directly used as a loss function for training the generator.

We use a very simple model. The generator uses a dense layer to transform the input noise into a 7x7 image with eight
channels. That is followed by two convolutional layers that upsample it first to 14x14, and finally to 28x28.

The discriminator does roughly the same thing in reverse. Two convolutional layers downsample the image first to
14x14, then to 7x7. A final dense layer produces a single number as output. In the last tutorial we used a sigmoid
activation to produce a number between 0 and 1 that could be interpreted as a probability. Since this is a WGAN, we
instead use a softplus activation. It produces an unbounded positive number that can be interpreted as a distance.

class DigitGAN(dc.models.WGAN):

def get_noise_input_shape(self):
return (10,)

def get_data_input_shapes(self):
return [(28, 28, 1)]

def create_generator(self):
return tf.keras.Sequential([
Dense(7*7*8, activation=tf.nn.relu),
Reshape((7, 7, 8)),
Conv2DTranspose(filters=16, kernel_size=5, strides=2, activation=tf.nn.relu, padding='same'),
Conv2DTranspose(filters=1, kernel_size=5, strides=2, activation=tf.sigmoid, padding='same')
])

def create_discriminator(self):
return tf.keras.Sequential([
Conv2D(filters=32, kernel_size=5, strides=2, activation=tf.nn.leaky_relu, padding='same'),
Conv2D(filters=64, kernel_size=5, strides=2, activation=tf.nn.leaky_relu, padding='same'),
Dense(1, activation=tf.math.softplus)
])

gan = DigitGAN(learning_rate=ExponentialDecay(0.001, 0.9, 5000))

Now to train it. As in the last tutorial, we write a generator to produce data. This time the data is coming from a dataset,
which we loop over 100 times.

One other difference is worth noting. When training a conventional GAN, it is important to keep the generator and
discriminator in balance thoughout training. If either one gets too far ahead, it becomes very difficult for the other one
to learn.

WGANs do not have this problem. In fact, the better the discriminator gets, the cleaner a signal it provides and the
easier it becomes for the generator to learn. We therefore specify generator_steps=0.2 so that it will only take one
step of training the generator for every five steps of training the discriminator. This tends to produce faster training and
better results.

def iterbatches(epochs):
for i in range(epochs):
for batch in dataset.iterbatches(batch_size=gan.batch_size):
yield {gan.data_inputs[0]: batch[0]}

gan.fit_gan(iterbatches(100), generator_steps=0.2, checkpoint_interval=5000)

Ending global_step 4999: generator average loss 0.340072, discriminator average loss -0.0234236
Ending global_step 9999: generator average loss 0.52308, discriminator average loss -0.00702729
Ending global_step 14999: generator average loss 0.572661, discriminator average loss -0.00635684
Ending global_step 19999: generator average loss 0.560454, discriminator average loss -0.00534357
Ending global_step 24999: generator average loss 0.556055, discriminator average loss -0.00620613
Ending global_step 29999: generator average loss 0.541958, discriminator average loss -0.00734233
Ending global_step 34999: generator average loss 0.540904, discriminator average loss -0.00736641
Ending global_step 39999: generator average loss 0.524298, discriminator average loss -0.00650514
Ending global_step 44999: generator average loss 0.503931, discriminator average loss -0.00563732
Ending global_step 49999: generator average loss 0.528964, discriminator average loss -0.00590612
Ending global_step 54999: generator average loss 0.510892, discriminator average loss -0.00562366
Ending global_step 59999: generator average loss 0.494756, discriminator average loss -0.00533636
TIMING: model fitting took 4197.860 s

Let's generate some data and see how the results look.

plot_digits(gan.predict_gan_generator(batch_size=16))

Not too bad. Many of the generated images look plausibly like handwritten digits. A larger model trained for a longer
time can do much better, of course.
Congratulations! Time to join the Community!
Congratulations on completing this tutorial notebook! If you enjoyed working through the tutorial, and want to continue
working with DeepChem, we encourage you to finish the rest of the tutorials in this series. You can also help the
DeepChem community in the following ways:

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

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The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Advanced model training using hyperopt
In the Advanced Model Training tutorial we have already taken a look into hyperparameter optimasation using
GridHyperparamOpt in the deepchem pacakge. In this tutorial, we will take a look into another hyperparameter tuning
library called hyperopt.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

Setup
To run DeepChem and Hyperopt within Colab, you'll need to run the following installation commands. You can of course
run this tutorial locally if you prefer. In that case, don't run these cells since they will download and install DeepChem
and Hyperopt in your local machine again.

!pip install deepchem

!pip install hyperopt

Collecting deepchem
Downloading deepchem-2.6.1-py3-none-any.whl (608 kB)

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Hyperparameter Optimization via hyperopt

Let's start by loading the HIV dataset. It classifies over 40,000 molecules based on whether they inhibit HIV replication.

import deepchem as dc
tasks, datasets, transformers = dc.molnet.load_hiv(featurizer='ECFP', split='scaffold')
train_dataset, valid_dataset, test_dataset = datasets

'split' is deprecated. Use 'splitter' instead.

Now, lets import the hyperopt library, which we will be using to fund the best parameters

from hyperopt import hp, fmin, tpe, Trials

Then we have to declare a dictionary with all the hyperparameters and their range that you will be tuning them in. This
dictionary will serve as the search space for the hyperopt. Some basic ways of declaring the ranges in the dictionary
are:

hp.choice('label',[choices]) : this is used to specify a list of choices

hp.uniform('label' ,low=low_value ,high=high_value) : this is used to specify a uniform distibution between the low
and high values. The values between them can be any real number, not necessaarily an integer.

Here, we are going to use a multitaskclassifier to classify the HIV dataset and hence the appropriate search space is as
follows.

search_space = {
'layer_sizes': hp.choice('layer_sizes',[[500], [1000], [2000],[1000,1000]]),
'dropouts': hp.uniform('dropout',low=0.2, high=0.5),
'learning_rate': hp.uniform('learning_rate',high=0.001, low=0.0001)
}

We should then declare a function to be minimized by the hyperopt. So, here we should use the function to minimize our
multitaskclassifier model. Additionally, we are using a validation callback to validate the classifier for every 1000 steps,
then we are passing the best score as the return. The metric used here is 'roc_auc_score', which needs to be maximized.
To maximize a non-negative value is equivalent to minimize its opposite number, hence we are returning the negative
of the validation score.

import tempfile
#tempfile is used to save the best checkpoint later in the program.

metric = dc.metrics.Metric(dc.metrics.roc_auc_score)

def fm(args):
save_dir = tempfile.mkdtemp()
model = dc.models.MultitaskClassifier(n_tasks=len(tasks),n_features=1024,layer_sizes=args['layer_sizes'],dropouts
#validation callback that saves the best checkpoint, i.e the one with the maximum score.
validation=dc.models.ValidationCallback(valid_dataset, 1000, [metric],save_dir=save_dir,transformers=transformers

model.fit(train_dataset, nb_epoch=25,callbacks=validation)

#restoring the best checkpoint and passing the negative of its validation score to be minimized.
model.restore(model_dir=save_dir)
valid_score = model.evaluate(valid_dataset, [metric], transformers)

return -1*valid_score['roc_auc_score']

Here, we are calling the fmin function of the hyperopt, where we pass on the function to be minimized, the algorithm to
be followed, max number of evals and a trials object. The Trials object is used to keep All hyperparameters, loss, and
other information, this means you can access them after running optimization. Also, trials can help you to save
important information and later load and then resume the optimization process.

Moreover, for the algorithm there are three choice which can be used without any additional configuration. they are :-

Random Search - rand.suggest

TPE (Tree Parzen Estimators) - tpe.suggest
Adaptive TPE - atpe.suggest

trials=Trials()
best = fmin(fm,
space= search_space,
algo=tpe.suggest,
max_evals=15,
trials = trials)

0%| | 0/15 [00:00<?, ?it/s, best loss: ?]Step 1000 validation: roc_auc_score=0.777648
Step 2000 validation: roc_auc_score=0.755485
Step 3000 validation: roc_auc_score=0.739519
Step 4000 validation: roc_auc_score=0.764756
Step 5000 validation: roc_auc_score=0.757006
Step 6000 validation: roc_auc_score=0.752609
Step 7000 validation: roc_auc_score=0.763002
Step 8000 validation: roc_auc_score=0.749202
7%|▋ | 1/15 [05:37<1:18:46, 337.58s/it, best loss: -0.7776476459925534]Step 1000 validation: roc_auc_s
core=0.750455
Step 2000 validation: roc_auc_score=0.783594
Step 3000 validation: roc_auc_score=0.775872
Step 4000 validation: roc_auc_score=0.768825
Step 5000 validation: roc_auc_score=0.769555
Step 6000 validation: roc_auc_score=0.765324
Step 7000 validation: roc_auc_score=0.771146
Step 8000 validation: roc_auc_score=0.760138
13%|█▎ | 2/15 [07:05<41:16, 190.51s/it, best loss: -0.7835939030962179] Step 1000 validation: roc_auc_s
core=0.744178
Step 2000 validation: roc_auc_score=0.765406
Step 3000 validation: roc_auc_score=0.76532
Step 4000 validation: roc_auc_score=0.769255
Step 5000 validation: roc_auc_score=0.77029
Step 6000 validation: roc_auc_score=0.768024
Step 7000 validation: roc_auc_score=0.764157
Step 8000 validation: roc_auc_score=0.756805
20%|██ | 3/15 [09:40<34:53, 174.42s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.714572
Step 2000 validation: roc_auc_score=0.770712
Step 3000 validation: roc_auc_score=0.777914
Step 4000 validation: roc_auc_score=0.76923
Step 5000 validation: roc_auc_score=0.774823
Step 6000 validation: roc_auc_score=0.775927
Step 7000 validation: roc_auc_score=0.777054
Step 8000 validation: roc_auc_score=0.778508
27%|██▋ | 4/15 [12:12<30:22, 165.66s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.743939
Step 2000 validation: roc_auc_score=0.759478
Step 3000 validation: roc_auc_score=0.738839
Step 4000 validation: roc_auc_score=0.751084
Step 5000 validation: roc_auc_score=0.740504
Step 6000 validation: roc_auc_score=0.753612
Step 7000 validation: roc_auc_score=0.71802
Step 8000 validation: roc_auc_score=0.761025
33%|███▎ | 5/15 [17:40<37:21, 224.16s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.74099
Step 2000 validation: roc_auc_score=0.767516
Step 3000 validation: roc_auc_score=0.767338
Step 4000 validation: roc_auc_score=0.775691
Step 5000 validation: roc_auc_score=0.768731
Step 6000 validation: roc_auc_score=0.755029
Step 7000 validation: roc_auc_score=0.767115
Step 8000 validation: roc_auc_score=0.764744
40%|████ | 6/15 [22:48<37:54, 252.71s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.713761
Step 2000 validation: roc_auc_score=0.759518
Step 3000 validation: roc_auc_score=0.765853
Step 4000 validation: roc_auc_score=0.771976
Step 5000 validation: roc_auc_score=0.772762
Step 6000 validation: roc_auc_score=0.773206
Step 7000 validation: roc_auc_score=0.775565
Step 8000 validation: roc_auc_score=0.768521
47%|████▋ | 7/15 [27:53<35:58, 269.84s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.717178
Step 2000 validation: roc_auc_score=0.754258
Step 3000 validation: roc_auc_score=0.767905
Step 4000 validation: roc_auc_score=0.762917
Step 5000 validation: roc_auc_score=0.766162
Step 6000 validation: roc_auc_score=0.767581
Step 7000 validation: roc_auc_score=0.770746
Step 8000 validation: roc_auc_score=0.77597
53%|█████▎ | 8/15 [30:36<27:29, 235.64s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.74314
Step 2000 validation: roc_auc_score=0.757408
Step 3000 validation: roc_auc_score=0.76668
Step 4000 validation: roc_auc_score=0.768104
Step 5000 validation: roc_auc_score=0.746377
Step 6000 validation: roc_auc_score=0.745282
Step 7000 validation: roc_auc_score=0.74113
Step 8000 validation: roc_auc_score=0.734482
60%|██████ | 9/15 [36:53<28:00, 280.04s/it, best loss: -0.7835939030962179]Step 1000 validation: roc_auc_sco
re=0.743204
Step 2000 validation: roc_auc_score=0.76912
Step 3000 validation: roc_auc_score=0.769981
Step 4000 validation: roc_auc_score=0.784163
Step 5000 validation: roc_auc_score=0.77536
Step 6000 validation: roc_auc_score=0.779237
Step 7000 validation: roc_auc_score=0.782344
Step 8000 validation: roc_auc_score=0.779085
67%|██████▋ | 10/15 [38:23<18:26, 221.33s/it, best loss: -0.7841634210268469]Step 1000 validation: roc_auc_sc
ore=0.743565
Step 2000 validation: roc_auc_score=0.765063
Step 3000 validation: roc_auc_score=0.75284
Step 4000 validation: roc_auc_score=0.759978
Step 5000 validation: roc_auc_score=0.74255
Step 6000 validation: roc_auc_score=0.721809
Step 7000 validation: roc_auc_score=0.729863
Step 8000 validation: roc_auc_score=0.73075
73%|███████▎ | 11/15 [44:07<17:15, 258.91s/it, best loss: -0.7841634210268469]Step 1000 validation: roc_auc_sc
ore=0.695949
Step 2000 validation: roc_auc_score=0.765082
Step 3000 validation: roc_auc_score=0.756256
Step 4000 validation: roc_auc_score=0.771923
Step 5000 validation: roc_auc_score=0.758841
Step 6000 validation: roc_auc_score=0.759393
Step 7000 validation: roc_auc_score=0.765971
Step 8000 validation: roc_auc_score=0.747064
80%|████████ | 12/15 [48:54<13:21, 267.23s/it, best loss: -0.7841634210268469]Step 1000 validation: roc_auc_sc
ore=0.757871
Step 2000 validation: roc_auc_score=0.765296
Step 3000 validation: roc_auc_score=0.769748
Step 4000 validation: roc_auc_score=0.776487
Step 5000 validation: roc_auc_score=0.775009
Step 6000 validation: roc_auc_score=0.779539
Step 7000 validation: roc_auc_score=0.763165
Step 8000 validation: roc_auc_score=0.772093
87%|████████▋ | 13/15 [50:22<07:06, 213.15s/it, best loss: -0.7841634210268469]Step 1000 validation: roc_auc_sc
ore=0.720166
Step 2000 validation: roc_auc_score=0.768489
Step 3000 validation: roc_auc_score=0.782853
Step 4000 validation: roc_auc_score=0.785556
Step 5000 validation: roc_auc_score=0.78583
Step 6000 validation: roc_auc_score=0.786569
Step 7000 validation: roc_auc_score=0.779249
Step 8000 validation: roc_auc_score=0.783423
93%|█████████▎| 14/15 [51:52<02:55, 175.93s/it, best loss: -0.7865693280913189]Step 1000 validation: roc_auc_sc
ore=0.743232
Step 2000 validation: roc_auc_score=0.762007
Step 3000 validation: roc_auc_score=0.771809
Step 4000 validation: roc_auc_score=0.755023
Step 5000 validation: roc_auc_score=0.769812
Step 6000 validation: roc_auc_score=0.769867
Step 7000 validation: roc_auc_score=0.777354
Step 8000 validation: roc_auc_score=0.775313
100%|██████████| 15/15 [56:47<00:00, 227.13s/it, best loss: -0.7865693280913189]

The code below is used to print the best hyperparameters found by the hyperopt.

print("Best: {}".format(best))

Best: {'dropout': 0.3749846096922802, 'layer_sizes': 0, 'learning_rate': 0.0007544819475363869}

The hyperparameter found here may not be necessarily the best one, but gives a general idea on which parameters are
effective. To get mroe accurate results, one has to increase the number of validation epochs and the epochs the model
fit. But doing so may increase the time in finding the best hyperparameters.

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Introduction to Gaussian Processes
In the world of cheminformatics and machine learning, models are often trees (random forest, XGBoost, etc.) or artifical
neural networks (deep neural networks, graph convolutional networks, etc.). These models are known as "Frequentist"
models. However, there is another category known as Bayesian models. Today we will be experimenting with a
Bayesian model implemented in scikit-learn known as gaussian processes (GP). For a deeper dive on GP, there is a great
tutorial paper on how GP works for regression. There is also an academic paper that applies GP to a real world problem.

As a short intro, GP allows us to build up our statistical model using an infinite number of Gaussian functions over our n-
dimensional space, where n is the number of features. However, we pick these functions based on how well they fit the
data we pass it. We end up with a statistical model built from an ensemble of Gaussian functions which can actually vary
quite a bit. The result is that for points we have trained the model on, the variance in our ensemble should be very low.
For test set points close to the training set points, the variance should be higher but still low as the ensemble was
picked to predict well in its neighborhood. For points far from the training set points, however, we did not pick our
ensemble of Gaussian functions to fit them so we'd expect the variance in our ensemble to be high. In this way, we end
up with a statistical model that allows for a natural generation of uncertainty.

Colab
This tutorial and the rest in the sequences are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
The first step is to get DeepChem up and running. We recommend using Google Colab to work through this tutorial
series. You'll need to run the following commands to get DeepChem installed on your colab notebook.

%pip install --pre deepchem

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v20210319222130)
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deepchem) (1.0.2)
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em) (1.19.1)
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hem) (1.3.1)
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hem) (1.1.0)
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em) (1.6.2)
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ages (from pandas->deepchem) (2.8.2)
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pandas->deepchem) (2021.3)
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es (from scikit-learn->deepchem) (2.2.0)

Gaussian Processes
As stated earlier, GP is already implemented in scikit-learn so we will be using DeepChem's scikit-learn wrapper.
SklearnModel is a subclass of DeepChem's Model class. It acts as a wrapper around a sklearn.base.BaseEstimator.

Here we import deepchem and the GP regressor model from sklearn.

import deepchem as dc
from sklearn.gaussian_process import GaussianProcessRegressor
from sklearn.gaussian_process.kernels import RBF, WhiteKernel

import numpy as np
import matplotlib.pyplot as plt

Loading data
Next we need a dataset that presents a regression problem. For this tutorial we will be using the BACE dataset from
MoleculeNet.

tasks, datasets, transformers = dc.molnet.load_bace_regression(featurizer='ecfp', splitter='random')

train_dataset, valid_dataset, test_dataset = datasets

I always like to get a close look at what the objects in my code are storing. We see that tasks is a list of tasks that we
are trying to predict. The transformer is a NormalizationTransformer that normalizes the outputs (y values) of the
dataset.

print(f'The tasks are: {tasks}')

print(f'The transformers are: {transformers}')
print(f'The transformer normalizes the outputs (y values): {transformers[0].transform_y}')

The tasks are: ['pIC50']

The transformers are: [<deepchem.trans.transformers.NormalizationTransformer object at 0x7fc04401b190>]
The transformer normalizes the outputs (y values): True

Here we see that the data has already been split into a training set, a validation set, and a test set. We will train the
model on the training set and test the accuracy of the model on the test set. If we were to do any hyperparameter
tuning, we would use the validation set. The split was ~80/10/10 train/valid/test.

print(train_dataset)
print(valid_dataset)
print(test_dataset)

Using the SklearnModel

Here we first create the model using the GaussianProcessRegressor we imported from sklearn. Then we wrap it in
DeepChem's SklearnModel. To learn more about the model, you can either read the sklearn API or run
help(GaussianProcessRegressor) in a code block.

As you see, the values I picked for the parameters seem awfully specific. This is because I needed to do some
hyperparameter tuning beforehand to get model that wasn't wildly overfitting the training set. You can learn more about
how I tuned the model in the Appendix at the end of this tutorial.

output_variance = 7.908735015054668
length_scale = 6.452349252677817
noise_level = 0.10475507755839343
kernel = output_variance**2 * RBF(length_scale=length_scale, length_scale_bounds='fixed') + WhiteKernel(noise_level
alpha = 4.989499481123432e-09

sklearn_gpr = GaussianProcessRegressor(kernel=kernel, alpha=alpha)

model = dc.models.SklearnModel(sklearn_gpr)

Then we fit our model to the data and see how it performs both on the training set and on the test set.

model.fit(train_dataset)
metric1 = dc.metrics.Metric(dc.metrics.mean_squared_error)
metric2 = dc.metrics.Metric(dc.metrics.r2_score)
print(f'Training set score: {model.evaluate(train_dataset, [metric1, metric2])}')
print(f'Test set score: {model.evaluate(test_dataset, [metric1, metric2])}')

Training set score: {'mean_squared_error': 0.0457129375800123, 'r2_score': 0.9542870624199877}

Test set score: {'mean_squared_error': 0.20503945381118496, 'r2_score': 0.7850242035806018}

Analyzing the Results

We can also visualize how well the predicted values match up to the measured values. First we need a function that
allows us to obtain both the mean predicted value and the standard deviation of the value. This is done by sampling 100
predictions from each set of inputs X and calculating the mean and standard deviation.

def predict_with_error(dc_model, X, y_transformer):

samples = model.model.sample_y(X, 100)
means = y_transformer.untransform(np.mean(samples, axis=1))
stds = y_transformer.y_stds[0] * np.std(samples, axis=1)

return means, stds

For our training set, we see a pretty good correlation between the measured values (x-axis) and the predicted values (y-
axis). Note that we use the transformer from earlier to untransform our predicted values.

y_meas_train = transformers[0].untransform(train_dataset.y)
y_pred_train, y_pred_train_stds = predict_with_error(model, train_dataset.X, transformers[0])

plt.xlim([2.5, 10.5])
plt.ylim([2.5, 10.5])
plt.scatter(y_meas_train, y_pred_train)

<matplotlib.collections.PathCollection at 0x7fc0431b45d0>

We now do the same for our test set. We see a fairly good correlation! However, it is certainly not as tight. This is
reflected in the difference between the R2 scores calculated above.

y_meas_test = transformers[0].untransform(test_dataset.y)
y_pred_test, y_pred_test_stds = predict_with_error(model, test_dataset.X, transformers[0])

plt.xlim([2.5, 10.5])
plt.ylim([2.5, 10.5])
plt.scatter(y_meas_test, y_pred_test)

<matplotlib.collections.PathCollection at 0x7fc04023b590>

We can also write a function to calculate how many of the predicted values fall within the predicted error range. This is
done by counting up how many samples have a true error smaller than its standard deviation calculated earlier. One
standard deviation is a 68% confidence interval.

def percent_within_std(y_meas, y_pred, y_std):

assert len(y_meas) == len(y_pred) and len(y_meas) == len(y_std), 'length of y_meas and y_pred must be the same'

count_within_error = 0
for i in range(len(y_meas)):
if abs(y_meas[i][0]-y_pred[i]) < y_std[i]:
count_within_error += 1

return count_within_error/len(y_meas)

For the train set, >90% of the samples are within a standard deviation. In comparison, only ~70% of the samples are
within a standard deviation for the test set. A standard deviation is a 68% confidence interval so we see that for the
training set, the uncertainty is close. However, this model overpredicts uncertainty on the training set.

percent_within_std(y_meas_train, y_pred_train, y_pred_train_stds)

0.9355371900826446

percent_within_std(y_meas_test, y_pred_test, y_pred_test_stds)

0.7368421052631579

We can also take a look at the distributions of the standard deviations for the test set predictions. We see a very roughly
Gaussian distribution in the predicted errors.

plt.hist(y_pred_test_stds)
plt.show()

For now, this is the end of our tutorial. We plan to follow up soon with a deeper dive into uncertainty estimation and in
particular, calibrated uncertainty estimation. We will see you then!

Appendix: Hyperparameter Optimization

As hyperparameter optimization is outside the scope of this tutorial, I will not explain how to use Optuna to tune
hyperparameters. But the code is still included for the sake of completeness.

%pip install optuna

import optuna

def get_model(trial):
output_variance = trial.suggest_float('output_variance', 0.1, 10, log=True)
length_scale = trial.suggest_float('length_scale', 1e-5, 1e5, log=True)
noise_level = trial.suggest_float('noise_level', 1e-5, 1e5, log=True)

params = {
'kernel': output_variance**2 * RBF(length_scale=length_scale, length_scale_bounds='fixed') + WhiteKernel(nois
'alpha': trial.suggest_float('alpha', 1e-12, 1e-5, log=True),
}

sklearn_gpr = GaussianProcessRegressor(**params)
return dc.models.SklearnModel(sklearn_gpr)

def objective(trial):
model = get_model(trial)
model.fit(train_dataset)

metric = dc.metrics.Metric(dc.metrics.mean_squared_error)
return model.evaluate(valid_dataset, [metric])['mean_squared_error']

study = optuna.create_study(direction='minimize')
study.optimize(objective, n_trials=100)

print(study.best_params)

{'output_variance': 0.38974570882583015, 'length_scale': 5.375387643239208, 'noise_level': 0.0016265333497286342

, 'alpha': 1.1273318360324618e-11}
Pytorch-Lightning Integration for DeepChem Models
In this tutorial we will go through how to setup a deepchem model inside the pytorch-lightning framework. Lightning is a
pytorch framework which simplifies the process of experimenting with pytorch models easier. A few key functionalities
offered by pytorch lightning which deepchem users can find useful are:

1. Multi-gpu training functionalities: pytorch-lightning provides easy multi-gpu, multi-node training. It also simplifies
the process of launching multi-gpu, multi-node jobs across different cluster infrastructure, e.g. AWS, slurm based
clusters.

2. Reducing boilerplate pytorch code: lightning takes care of details like, optimizer.zero_grad(), model.train(),
model.eval() . Lightning also provides experiment logging functionality, for e.g. irrespective of training on CPU,
GPU, multi-nodes the user can use the method self.log inside the trainer and it will appropriately log the metrics.

3. Features that can speed up training: half-precision training, gradient checkpointing, code profiling.

Open in Colab

Setup
This notebook assumes that you have already installed deepchem, if you have not follow the instructions at the
deepchem installation page: https://deepchem.readthedocs.io/en/latest/get_started/installation.html.
Install pytorch lightning following the instructions on lightning's home page: https://www.pytorchlightning.ai/

!pip install --pre deepchem

!pip install pytorch_lightning

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Import the relevant packages.

import deepchem as dc
from deepchem.models import GCNModel
import pytorch_lightning as pl
import torch
from torch.nn import functional as F
from torch import nn
import pytorch_lightning as pl
from pytorch_lightning.core.lightning import LightningModule
from torch.optim import Adam
import numpy as np
import torch

Deepchem Example
Below we show an example of a Graph Convolution Network (GCN). Note that this is a simple example which uses a
GCNModel to predict the label from an input sequence. We do not showcase the complete functionality of deepchem in
this example as we want to restructure the deepchem code and adapt it so that it can be easily plugged into pytorch-
lightning. This example was inspired from the GCNModel documentation present here.

Prepare the dataset: for training our deepchem models we need a dataset that we can use to train the model. Below
we prepare a sample dataset for the purposes of this tutorial. Below we also directly use the featurized to encode
examples for the dataset.

smiles = ["C1CCC1", "CCC"]

labels = [0., 1.]
featurizer = dc.feat.MolGraphConvFeaturizer()
X = featurizer.featurize(smiles)
dataset = dc.data.NumpyDataset(X=X, y=labels)

Setup the model: now we initialize the Graph Convolutional Network model that we will use in our training.

model = GCNModel(
mode='classification',
n_tasks=1,
batch_size=2,
learning_rate=0.001
)

[16:00:37] /Users/princychahal/Documents/github/dgl/src/runtime/tensordispatch.cc:43: TensorDispatcher: dlopen f

ailed: Using backend: pytorch
dlopen(/Users/princychahal/mambaforge/envs/keras_try_5/lib/python3.8/site-packages/dgl-0.8-py3.8-macosx-11.0-arm
64.egg/dgl/tensoradapter/pytorch/libtensoradapter_pytorch_1.10.2.dylib, 1): image not found

Train the model: fit the model on our training dataset, also specify the number of epochs to run.

loss = model.fit(dataset, nb_epoch=5)

print(loss)

0.18830760717391967
/Users/princychahal/mambaforge/envs/keras_try_5/lib/python3.8/site-packages/torch/autocast_mode.py:141: UserWarn
ing: User provided device_type of 'cuda', but CUDA is not available. Disabling
warnings.warn('User provided device_type of \'cuda\', but CUDA is not available. Disabling')

Pytorch-Lightning + Deepchem example

Now we will look at an example of the GCN model adapt for Pytorch-Lightning. For using Pytorch-Lightning there are two
important components:

1. LightningDataModule : This module defines who the data is prepared and fed into the model so that the model
can use it for training. The module defines the train dataloader function which are directly used by the trainer to
generate data for the LightningModule . To learn more about the LightningDataModule refer to the
datamodules documentation.
2. LightningModule : This module defines the training, validation steps for our model. We can use this module to
initialize our model based on the hyperparameters. There are a number of boilerplate functions which we use
directly to track our experiments, for example we can save all the hyperparameters that we used for training using
the self.save_hyperparameters() method. For more details on how to use this module refer to the
lightningmodules documentation.

Setup the torch dataset: Note that here we need to create a custome SmilesDataset so that we can easily
interface with the deepchem featurizers. For this interface we need to define a collate method so that we can create
batches for the dataset.

# prepare LightningDataModule
class SmilesDataset(torch.utils.data.Dataset):
def __init__(self, smiles, labels):
assert len(smiles) == len(labels)
featurizer = dc.feat.MolGraphConvFeaturizer()
X = featurizer.featurize(smiles)
self._samples = dc.data.NumpyDataset(X=X, y=labels)

def __len__(self):
return len(self._samples)

def getitem(self, index):

return (
self._samples.X[index],
self._samples.y[index],
self._samples.w[index],
)

class SmilesDatasetBatch:
def __init__(self, batch):
X = [np.array([b[0] for b in batch])]
y = [np.array([b[1] for b in batch])]
w = [np.array([b[2] for b in batch])]
self.batch_list = [X, y, w]

def collate_smiles_dataset_wrapper(batch):
return SmilesDatasetBatch(batch)

Create the GCN specific lightning module: in this part we use an object of the SmilesDataset created above to
create the SmilesDatasetModule

class SmilesDatasetModule(pl.LightningDataModule):
def __init__(self, train_smiles, train_labels, batch_size):
super().__init__()
self._train_smiles = train_smiles
self._train_labels = train_labels
self._batch_size = batch_size

def setup(self, stage):

self.train_dataset = SmilesDataset(
self._train_smiles,
self._train_labels,
)

def train_dataloader(self):
return torch.utils.data.DataLoader(
self.train_dataset,
batch_size=self._batch_size,
collate_fn=collate_smiles_dataset_wrapper,
shuffle=True,
)

Create the lightning module: in this part we create the GCN specific lightning module. This class specifies the logic
flow for the training step. We also create the required models, optimizers and losses for the training flow.

# prepare the LightningModule

class GCNModule(pl.LightningModule):
def __init__(self, mode, n_tasks, learning_rate):
super().__init__()
self.save_hyperparameters(
"mode",
"n_tasks",
"learning_rate",
)
self.gcn_model = GCNModel(
mode=self.hparams.mode,
n_tasks=self.hparams.n_tasks,
learning_rate=self.hparams.learning_rate,
)
self.pt_model = self.gcn_model.model
self.loss = self.gcn_model._loss_fn

def configure_optimizers(self):
return self.gcn_model.optimizer._create_pytorch_optimizer(
self.pt_model.parameters(),
)

def training_step(self, batch, batch_idx):

batch = batch.batch_list
inputs, labels, weights = self.gcn_model._prepare_batch(batch)
outputs = self.pt_model(inputs)

if isinstance(outputs, torch.Tensor):
outputs = [outputs]
if self.gcn_model._loss_outputs is not None:
outputs = [outputs[i] for i in self.gcn_model._loss_outputs]

loss_outputs = self.loss(outputs, labels, weights)

self.log(
"train_loss",
loss_outputs,
on_epoch=True,
sync_dist=True,
reduce_fx="mean",
prog_bar=True,
)

return loss_outputs

Create the relevant objects

# create module objects

smiles_datasetmodule = SmilesDatasetModule(
train_smiles=["C1CCC1", "CCC", "C1CCC1", "CCC", "C1CCC1", "CCC", "C1CCC1", "CCC", "C1CCC1", "CCC"],
train_labels=[0., 1., 0., 1., 0., 1., 0., 1., 0., 1.],
batch_size=2,
)

gcnmodule = GCNModule(
mode="classification",
n_tasks=1,
learning_rate=1e-3,
)

Lightning Trainer
Trainer is the wrapper which builds on top of the LightningDataModule and LightningModule . When constructing
the lightning trainer you can also specify the number of epochs, max-steps to run, number of GPUs, number of nodes to
be used for trainer. Lightning trainer acts as a wrapper over your distributed training setup and this way you are able to
build your models in a way you would build them in a simple way for your local runs.

trainer = pl.Trainer(
max_epochs=5,
)

GPU available: False, used: False

TPU available: False, using: 0 TPU cores
IPU available: False, using: 0 IPUs

Call the fit function to run model training

# train
trainer.fit(
model=gcnmodule,
datamodule=smiles_datasetmodule,
)

| Name | Type | Params

----------------------------------
0 | pt_model | GCN | 29.4 K
----------------------------------
29.4 K Trainable params
0 Non-trainable params
29.4 K Total params
0.118 Total estimated model params size (MB)
/Users/princychahal/mambaforge/envs/keras_try_5/lib/python3.8/site-packages/pytorch_lightning/trainer/data_loadi
ng.py:132: UserWarning: The dataloader, train_dataloader, does not have many workers which may be a bottleneck.
Consider increasing the value of the `num_workers` argument` (try 8 which is the number of cpus on this machine)
in the `DataLoader` init to improve performance.
rank_zero_warn(
/Users/princychahal/mambaforge/envs/keras_try_5/lib/python3.8/site-packages/pytorch_lightning/trainer/data_loadi
ng.py:428: UserWarning: The number of training samples (5) is smaller than the logging interval Trainer(log_ever
y_n_steps=50). Set a lower value for log_every_n_steps if you want to see logs for the training epoch.
rank_zero_warn(
Training: 0it [00:00, ?it/s]
Compiling Deepchem Torch Models
Deep Learning models typically involve millions or even billions of parameters (as in the case of LLMs) that need to be
fine-tuned through an iterative training processes. During training, these models process vast amounts of data to learn
patterns and features effectively. This data-intensive nature, combined with the computational complexity of operations
like matrix multiplications and backpropagation, leads to lengthy training times that can span days, weeks, or even
months on standard hardware. Additionally, the need for multiple training runs to experiment with the different model
and hyperparameter configurations further extends the overall development time.

Effective optimization techniques can significantly reduce training times, lower computational costs, and improve model
performance. This makes optimization particularly crucial in research and industrial settings where faster iterations can
accelerate scientific discoveries, product development, and the deployment of AI solutions. Moreover, as models grow
larger and more sophisticated, optimization plays a vital role in making advanced AI accessible and practical for a wider
range of applications and environments.

To address the need for optimization of Deep Larning models and as an improvement over existing methods, PyTorch
introduced the torch.compile() function in PyTorch 2.0 to allow faster training and inference of the models.
torch.compile() works by compiling PyTorch code into optimised kernels using a JIT(Just in Time) compiler. Different
models show varying levels of improvement in run times depending on their architecture and batch size when compiled.
Compared to existing methods like TorchScript or FX tracing, compile() also offers advantages such as the ability to
handle arbitrary Python code and conditional graph-breaking flow of the inputs to the models. This allows compile() to
work with minimal or no code modification to the model.

DeepChem has builtin support for compiling PyTorch models using torch.compile() and using this feature, users can
efficiently run PyTorch models and achieve significant performance gains. This tutorial contains the steps for compiling
DeepChem PyTorch models, benchmarking and evaluating their performance with the uncompiled models.

NOTE: DeepChem contains many models with varying architecture and complexity. Not all models will show
significant improvements in run times when compiled. It is recommended to test the models with and
without compilation to determine the performance improvements.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

Compilation Process
This section gives an introductory explanation about the compilation process of PyTorch models and assumes prior
knowledge about forward pass, backward pass and computational graphs in neural networks. If you're unfamiliar with
these concepts, you can refer to these slides for a basic understanding. Alternatively, you can proceed to the next
section to learn how to compile and benchmark DeepChem models without delving into the internal details of the
compilation process.
Image taken from PyTorch2.0 Introductory Blog

The compilation process is split into multiple steps which uses many new technologies that were introduced in PyTorch
2.0. The process is as follows:

1. Graph Acquisition: During the compilation process, TorchDynamo and AOTAutograd are used for capturing the
forward and backward pass graphs respectively. AOTAutograd allows the backward graph to be captured ahead of
time without needing a backward pass to be performed.

2. Graph Lowering: The captured graph that could be composed of the 2000+ PyTorch operators is lowered into a
collection of ~250 Prim and ~750 ATen operators.

3. Graph Compilation: In this step optimised low-level kernels are generated for the target accelerator using a
suitable backend compiler. TorchInductor is the default backend compiler used for this purpose.

Deepchem uses the torch.compile() function that implements all the above steps internally to compile the models.
The compiled model can be used for training, evaluation and inference.

For more information on the compilation process, refer to PyTorch2.0 Introductory Blog that does a deep dive into the
compilation process, technical decisions and future features for the compile function. You can also refer to the
Huggingface blog, Optimize inference using torch.compile() that benchmarks many common PyTorch models and shows
the performance improvements when compiled.

Compiling Models
The compile function is only available in DeepChem for models that use PyTorch as the backend (i.e inherits
TorchModel class). You can see the complete list of models that are available in DeepChem and their backends in the
DeepChem Documentation here.

This tutorial contains the steps to load a DeepChem model, compile it and evaluate the performance improvements
when compiled for both training and inference. Refer to the documentation of DeepChem's compile function to read
more about the different parameters you can pass to the function and their usage.

If you just want to compile the model, you can add the line model.compile() after initialising the model. You DO NOT
have to make any changes to the rest of your code.

Some of the things to keep in mind when compiling models are:

1. Selecting the right mode: The modes can be default , reduce-overhead , max-autotune or max-autotune-
no-cudagraphs . Out of this reduce-overhead and max-autotune modes requires triton to be installed. Refer
to the PyTorch docs on torch.compile for more information on the modes.

2. Setting fullgraph parameter: If True (default False ), torch.compile will require that the entire function be
capturable into a single graph. If this is not possible (that is, if there are graph breaks), then the function will raise
an error.

3. Experimenting with different parameter configuration: Different parameter configurations can give different
speedups based on the model, batch size and the device used for training/inference. Experiment with a few
parameter combinations to check which one gives better results.

In this tutorial, we will be using DMPNN model and Freesolv Dataset for training and inference of the models.

!pip install --pre deepchem

!pip install torch_geometric #required for DMPNN model
!pip install triton #required for reduce-overhead mode

Collecting deepchem
Downloading deepchem-2.8.1.dev20240624214143-py3-none-any.whl (1.1 MB)
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Successfully installed deepchem-2.8.1.dev20240624214143 rdkit-2024.3.1
Collecting torch_geometric
Downloading torch_geometric-2.5.3-py3-none-any.whl (1.1 MB)
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import torch

import datetime
import numpy as np
import deepchem as dc

import matplotlib.pyplot as plt

WARNING:deepchem.feat.molecule_featurizers.rdkit_descriptors:No normalization for SPS. Feature removed!

WARNING:deepchem.feat.molecule_featurizers.rdkit_descriptors:No normalization for AvgIpc. Feature removed!
WARNING:tensorflow:From /usr/local/lib/python3.10/dist-packages/tensorflow/python/util/deprecation.py:588: calli
ng function (from tensorflow.python.eager.polymorphic_function.polymorphic_function) with experimental_relax_sha
pes is deprecated and will be removed in a future version.
Instructions for updating:
experimental_relax_shapes is deprecated, use reduce_retracing instead
WARNING:deepchem.models.torch_models:Skipped loading modules with pytorch-geometric dependency, missing a depend
ency. No module named 'dgl'
WARNING:deepchem.models:Skipped loading modules with pytorch-lightning dependency, missing a dependency. No modu
le named 'lightning'
WARNING:deepchem.models:Skipped loading some Jax models, missing a dependency. No module named 'haiku'

torch._dynamo.config.cache_size_limit = 64

tasks, datasets, transformers = dc.molnet.load_freesolv(featurizer=dc.feat.DMPNNFeaturizer(), splitter='random')

train_dataset, valid_dataset, test_dataset = datasets
len(train_dataset), len(valid_dataset), len(test_dataset)

model = dc.models.DMPNNModel()

The below line is the only addition you have to make to the code for compiling the model. You can pass in the other
arguments too to the compile() function if they are required.

model.compile()

/usr/lib/python3.10/multiprocessing/popen_fork.py:66: RuntimeWarning: os.fork() was called. os.fork() is incompa

tible with multithreaded code, and JAX is multithreaded, so this will likely lead to a deadlock.
self.pid = os.fork()

model.fit(train_dataset, nb_epoch=10)

metrics = [dc.metrics.Metric(dc.metrics.mean_squared_error)]
print(f"Training MSE: {model.evaluate(train_dataset, metrics=metrics)}")
print(f"Validation MSE: {model.evaluate(valid_dataset, metrics=metrics)}")
print(f"Test MSE: {model.evaluate(test_dataset, metrics=metrics)}")

Training MSE: {'mean_squared_error': 0.04699941161198689}

Validation MSE: {'mean_squared_error': 0.18010469643557037}
Test MSE: {'mean_squared_error': 0.043559911545479245}

Benchmarking model Speedups

This section contains the steps for benchmarking the performance of models after compilation process for both training
and inference. We are using the same model(DMPNN) and dataset(FreSolv) in this section too. The steps for compilation
and benchmarking is same for other models as well.

To account for the initial performance overhead of kernel compilation in compiled models, median values are employed
as the performance metric throughout the tutorial for calculating speedup.

The below two functions, time_torch_function and get_time_track_callback can be used for tracking the time
taken for inference and training respectively.

The implementation of time_torch_function is taken from the PyTorch official torch.compile tutorial here.

We use get_time_track_callback to make a callback that can track the time taken for each batch during training as
DeepChem does not provide a direct way to track the time taken per batch during training. We can use this callback by
passing it as an argument to model.fit() function.

def time_torch_function(fn):
start = torch.cuda.Event(enable_timing=True)
end = torch.cuda.Event(enable_timing=True)
start.record()
result = fn()
end.record()
torch.cuda.synchronize()
return result, start.elapsed_time(end) / 1000

track_dict = {}
prev_time_dict = {}
def get_time_track_callback(track_dict, track_name, track_interval):
track_dict[track_name] = []
prev_time_dict[track_name] = datetime.datetime.now()
def callback(model, step):
if step % track_interval == 0:
elapsed_time = datetime.datetime.now() - prev_time_dict[track_name]
track_dict[track_name].append(elapsed_time.total_seconds())
prev_time_dict[track_name] = datetime.datetime.now()
return callback

Tracking Training Time

model = dc.models.DMPNNModel()
model_compiled = dc.models.DMPNNModel()
model_compiled.compile(mode='reduce-overhead')

track_interval = 20
eager_dict_name = "eager_train"
compiled_dict_name = "compiled_train"

eager_train_callback = get_time_track_callback(track_dict, eager_dict_name, track_interval)

model.fit(train_dataset, nb_epoch=10, callbacks=[eager_train_callback])

compiled_train_callback = get_time_track_callback(track_dict, compiled_dict_name, track_interval)

model_compiled.fit(train_dataset, nb_epoch=10, callbacks=[compiled_train_callback])

0.06506308714548746

eager_train_times = track_dict[eager_dict_name]
compiled_train_times = track_dict[compiled_dict_name]

print(f"Eager Times (first 15): {[f'{t:.3f}' for t in eager_train_times[:15]]}")

print(f"Compiled Times (first 15): {[f'{t:.3f}' for t in compiled_train_times[:15]]}")
print(f"Total Eager Time: {sum(eager_train_times)}")
print(f"Total Compiled Time: {sum(compiled_train_times)}")
print(f"Eager Median: {np.median(eager_train_times)}")
print(f"Compiled Median: {np.median(compiled_train_times)}")
print(f"Median Speedup: {((np.median(eager_train_times) / np.median(compiled_train_times)) - 1) * 100:.2f}%")

Eager Times (first 15): ['1.067', '0.112', '0.093', '0.097', '0.102', '0.098', '0.095', '0.097', '0.099', '0.098
', '0.097', '0.103', '0.095', '0.103', '0.096']
Compiled Times (first 15): ['29.184', '21.463', '11.503', '13.742', '1.951', '5.595', '7.568', '8.201', '7.761',
'0.083', '7.087', '2.421', '1.961', '0.079', '1.948']
Total Eager Time: 29.176121000000023
Total Compiled Time: 243.32460400000022
Eager Median: 0.100118
Compiled Median: 0.0843535
Median Speedup: 18.69%

x_vals = np.arange(1, len(eager_train_times) + 1) * track_interval

plt.plot(x_vals, eager_train_times, label="Eager")
plt.plot(x_vals, compiled_train_times, label="Compiled")
plt.yscale('log', base= 10)
plt.ylabel('Time (s)')
plt.xlabel('Batch Iteration')
plt.legend()
plt.show()
Looking at the graph, there is a significant difference in the time taken for the compiled and uncompiled versions of the
model for the starting many steps. After that the time taken by the compiled model stabilises below the uncompiled
model. This is because the compilation is done JIT when the model is first run and the optimized kernels are generated
after a few passes.

Tracking Inference Time

model = dc.models.DMPNNModel()
model_compiled = dc.models.DMPNNModel()
model_compiled.compile(mode='reduce-overhead')

iters = 100

eager_predict_times = []
compiled_predict_times = []

for i in range(iters):
for X, y, w, ids in test_dataset.iterbatches(64, pad_batches=True):
with torch.no_grad():
_, eager_time = time_torch_function(lambda: model.predict_on_batch(X))
_, compiled_time = time_torch_function(lambda: model_compiled.predict_on_batch(X))

eager_predict_times.append(eager_time)
compiled_predict_times.append(compiled_time)

print(f"Eager Times (first 15): {[f'{t:.3f}' for t in eager_predict_times[:15]]}")

print(f"Compiled Times (first 15): {[f'{t:.3f}' for t in compiled_predict_times[:15]]}")
print(f"Total Eager Time: {sum(eager_predict_times)}")
print(f"Total Compiled Time: {sum(compiled_predict_times)}")
print(f"Eager Median: {np.median(eager_predict_times)}")
print(f"Compiled Median: {np.median(compiled_predict_times)}")
print(f"Median Speedup: {((np.median(eager_predict_times) / np.median(compiled_predict_times)) - 1) * 100:.2f}%")

Eager Times (first 15): ['0.170', '0.173', '0.161', '0.160', '0.160', '0.165', '0.158', '0.159', '0.164', '0.161
', '0.162', '0.154', '0.159', '0.161', '0.162']
Compiled Times (first 15): ['47.617', '1.168', '26.927', '0.127', '0.134', '0.138', '0.130', '0.130', '0.133', '
0.125', '0.130', '0.132', '0.139', '0.128', '0.133']
Total Eager Time: 35.297711242675796
Total Compiled Time: 104.20891365814221
Eager Median: 0.1617226104736328
Compiled Median: 0.1332385482788086
Median Speedup: 21.38%

plt.plot(eager_predict_times, label= "Eager")

plt.plot(compiled_predict_times, label= "Compiled")
plt.ylabel('Time (s)')
plt.xlabel('Batch Iteration')
plt.yscale('log', base= 10)
plt.legend()

<matplotlib.legend.Legend at 0x7c7a040c9c30>
As with the results we got training, the first few runs for inference also takes significantly more time due to the same
reason as mentioned before.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

We can now import the deepchem package to play with.

import deepchem as dc
dc.__version__

'2.4.0-rc1.dev'

Let's take a look at a dataset that has been featurized with ECFP.

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer='ECFP')

train_dataset, valid_dataset, test_dataset = datasets
print(train_dataset)

Let's also take a look at the weights array.

Training a Model on Fingerprints

model = dc.models.MultitaskClassifier(n_tasks=12, n_features=1024, layer_sizes=[1000])

Let's train and evaluate the model.

import numpy as np

training set score: {'roc_auc_score': 0.9550063590563469}

test set score: {'roc_auc_score': 0.7781819573695475}

Not bad performance for such a simple model and featurization. More sophisticated models do slightly better on this
dataset, but not enormously better.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

@manual{Intro4,
title={Molecular Fingerprints},
organization={DeepChem},
author={Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Molecular_Fingerprints.ipyn
year={2021},
}
Going Deeper On Molecular Featurizations
One of the most important steps of doing machine learning on molecular data is transforming the data into a form
amenable to the application of learning algorithms. This process is broadly called "featurization" and involves turning a
molecule into a vector or tensor of some sort. There are a number of different ways of doing that, and the choice of
featurization is often dependent on the problem at hand. We have already seen two such methods: molecular
fingerprints, and ConvMol objects for use with graph convolutions. In this tutorial we will look at some of the others.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install -qq --pre deepchem

import deepchem
import warnings
warnings.filterwarnings('ignore')
deepchem.__version__

'2.6.0.dev'

Featurizers
In DeepChem, a method of featurizing a molecule (or any other sort of input) is defined by a Featurizer object. There
are three different ways of using featurizers.

2. You also can create a Featurizer and directly apply it to molecules. For example:

import deepchem as dc

featurizer = dc.feat.CircularFingerprint()
print(featurizer(['CC', 'CCC', 'CCO']))

[[0. 0. 0. ... 0. 0. 0.]

3. When creating a new dataset with the DataLoader framework, you can specify a Featurizer to use for processing the
data. We will see this in a future tutorial.

Let's print the values of the first ten descriptors for propane.

from rdkit.Chem.Descriptors import descList

Of course, there are many more descriptors than this.

print('The number of descriptors present is: ', len(features))

The number of descriptors present is: 210

WeaveFeaturizer and MolGraphConvFeaturizer

The Coulomb matrix is one popular featurization for molecular conformations. Recall that the electrostatic Coulomb
interaction between two charges is proportional to

where

and

are the charges and

is the distance between them. For a molecule with

atoms, the Coulomb matrix is a

from rdkit import Chem

It only found a single conformer. This shouldn't be surprising, since propane is a very small molecule with hardly any
flexibility. Let's try adding another carbon.

butane_mol = generator.generate_conformers(Chem.MolFromSmiles('CCCC'))
print("Number of available conformers for butane: ", len(butane_mol.GetConformers()))

Number of available conformers for butane: 3

Now we can create a Coulomb matrix for our molecule.

eigenvalues instead of an

matrix), so models will be more limited in what they can learn.

coulomb_mat_eig = dc.feat.CoulombMatrixEig(max_atoms=20)
features = coulomb_mat_eig(propane_mol)
print(features)

[[60.07620303 29.62963149 22.75497781 0.5713786 0.28781332 0.28548338

0.27558187 0.18163794 0.17460999 0.17059719 0.16640098 0.
0. 0. 0. 0. 0. 0.
0. 0. ]]

SMILES Tokenization and Numericalization

We will use DeepChem's BasicSmilesTokenizer and the Tox21 dataset from MoleculeNet to demonstrate the process
of tokenizing SMILES.

import numpy as np

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer="Raw")

train_dataset, valid_dataset, test_dataset = datasets
print(train_dataset)

We loaded the datasets with featurizer="Raw" . Now we obtain the SMILES from their ids attributes.

train_smiles = train_dataset.ids
valid_smiles = valid_dataset.ids
test_smiles = test_dataset.ids
print(train_smiles[:5])

['CC(O)(P(=O)(O)O)P(=O)(O)O' 'CC(C)(C)OOC(C)(C)CCC(C)(C)OOC(C)(C)C'
'OC[C@H](O)[C@@H](O)[C@H](O)CO'
'CCCCCCCC(=O)[O-].CCCCCCCC(=O)[O-].[Zn+2]' 'CC(C)COC(=O)C(C)C']

Next we define our tokenizer and map it onto all our data to convert the SMILES strings into lists of tokens. The
BasicSmilesTokenizer breaks down SMILES roughly at atom level.

['C', 'C', '(', 'O', ')', '(', 'P', '(', '=', 'O', ')', '(', 'O', ')', 'O', ')', 'P', '(', '=', 'O', ')', '(', '
O', ')', 'O']
6264

flatten = lambda l: [item for items in l for item in items]

all_toks = flatten(train_tok) + flatten(valid_tok) + flatten(test_tok)

vocab = sorted(set(all_toks + [""]))
print(vocab[:12], "...", vocab[-12:])
len(vocab)

['', '#', '(', ')', '-', '.', '/', '1', '2', '3', '4', '5'] ... ['[n+]', '[n-]', '[nH+]', '[nH]', '[o+]', '[s+]'
, '[se]', '\\', 'c', 'n', 'o', 's']
128

str2int = {s:i for i, s in enumerate(vocab)}

int2str = {i:s for i, s in enumerate(vocab)}
print(f"str2int: {dict(list(str2int.items())[:5])} ...")
print(f"int2str: {dict(list(int2str.items())[:5])} ...")

str2int: {'': 0, '#': 1, '(': 2, ')': 3, '-': 4} ...

int2str: {0: '', 1: '#', 2: '(', 3: ')', 4: '-'} ...

encode = lambda s: [str2int[tok] for tok in s]

decode = lambda i: [int2str[num] for num in i]
print(train_smiles[0])
print(encode(train_tok[0]))
print("".join(decode(encode(train_tok[0]))))

CC(O)(P(=O)(O)O)P(=O)(O)O
[19, 19, 2, 24, 3, 2, 25, 2, 16, 24, 3, 2, 24, 3, 24, 3, 25, 2, 16, 24, 3, 2, 24, 3, 24]
CC(O)(P(=O)(O)O)P(=O)(O)O

train_num = list(map(encode, train_tok))

valid_num = list(map(encode, valid_tok))
test_num = list(map(encode, test_tok))
print(train_num[0])

[19, 19, 2, 24, 3, 2, 25, 2, 16, 24, 3, 2, 24, 3, 24, 3, 25, 2, 16, 24, 3, 2, 24, 3, 24]

max_len = max(map(len, train_num + valid_num + test_num))

max_len

240

The longest sequence across all Tox21 datasets has length 240 , so we use that as our fixed length. We create a
zero_pad function, map it to all numericalized SMILES, and turn them into np.array s.

zero_pad = lambda x: x + [0] * (max_len - len(x))

train_numpad = np.array(list(map(zero_pad, train_num)))

valid_numpad = np.array(list(map(zero_pad, valid_num)))
test_numpad = np.array(list(map(zero_pad, test_num)))
train_numpad

array([[19, 19, 2, ..., 0, 0, 0],

idx = np.random.randint(0, train_numpad.shape[0], 1).item()

print(train_smiles[idx])
print("".join(decode(train_numpad[idx])))

Cc1cc(C(C)(C)c2ccc(O)c(C)c2)ccc1O
Cc1cc(C(C)(C)c2ccc(O)c(C)c2)ccc1O

def tokenize_smiles(x, vocab, max_len):

class SmilesFeaturizer(dc.feat.Featurizer):
def __init__(self, feat_func, vocab, max_len):
self.feat_func = feat_func
self.vocab = vocab
self.max_len = max_len

def _featurize(self, x):

return self.feat_func(x, self.vocab, self.max_len)

smiles_featurizer = SmilesFeaturizer(tokenize_smiles, vocab, max_len)

Finally, we use the smiles_featurizer to create new Tox21 datasets that contain tokenized and numericalized
SMILES in their X attribute.

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer=smiles_featurizer)

print(datasets[0].X)

[09:24:48] WARNING: not removing hydrogen atom without neighbors

[[19 19 2 ... 0 0 0]
[19 19 2 ... 0 0 0]
[24 19 42 ... 0 0 0]
...
[24 16 19 ... 0 0 0]
[19 19 2 ... 0 0 0]
[19 19 2 ... 0 0 0]]

The datasets are now ready to be used with your custom DeepChem sequence model. Don't forget to wrap your model
into the appropriate DeepChem model class.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Intro7,
title={Going Deeper on Molecular Featurizations},
organization={DeepChem},
author={Ramsundar, Bharath},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Going_Deeper_on_Molecular_F
year={2021},
}
Learning Unsupervised Embeddings for Molecules
In this tutorial, we will use a SeqToSeq model to generate fingerprints for classifying molecules. This is based on the
following paper, although some of the implementation details are different: Xu et al., "Seq2seq Fingerprint: An
Unsupervised Deep Molecular Embedding for Drug Discovery" (https://doi.org/10.1145/3107411.3107424).

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

Learning Embeddings with SeqToSeq

Many types of models require their inputs to have a fixed shape. Since molecules can vary widely in the numbers of
atoms and bonds they contain, this makes it hard to apply those models to them. We need a way of generating a fixed
length "fingerprint" for each molecule. Various ways of doing this have been designed, such as the Extended-
Connectivity Fingerprints (ECFPs) we used in earlier tutorials. But in this example, instead of designing a fingerprint by
hand, we will let a SeqToSeq model learn its own method of creating fingerprints.

A SeqToSeq model performs sequence to sequence translation. For example, they are often used to translate text from
one language to another. It consists of two parts called the "encoder" and "decoder". The encoder is a stack of recurrent
layers. The input sequence is fed into it, one token at a time, and it generates a fixed length vector called the
"embedding vector". The decoder is another stack of recurrent layers that performs the inverse operation: it takes the
embedding vector as input, and generates the output sequence. By training it on appropriately chosen input/output
pairs, you can create a model that performs many sorts of transformations.

In this case, we will use SMILES strings describing molecules as the input sequences. We will train the model as an
autoencoder, so it tries to make the output sequences identical to the input sequences. For that to work, the encoder
must create embedding vectors that contain all information from the original sequence. That's exactly what we want in
a fingerprint, so perhaps those embedding vectors will then be useful as a way to represent molecules in other models!

Let's start by loading the data. We will use the MUV dataset. It includes 74,501 molecules in the training set, and 9313
molecules in the validation set, so it gives us plenty of SMILES strings to work with.

import deepchem as dc
tasks, datasets, transformers = dc.molnet.load_muv(split='stratified')
train_dataset, valid_dataset, test_dataset = datasets
train_smiles = train_dataset.ids
valid_smiles = valid_dataset.ids

We need to define the "alphabet" for our SeqToSeq model, the list of all tokens that can appear in sequences. (It's also
possible for input and output sequences to have different alphabets, but since we're training it as an autoencoder,
they're identical in this case.) Make a list of every character that appears in any training sequence.

tokens = set()
for s in train_smiles:
tokens = tokens.union(set(c for c in s))
tokens = sorted(list(tokens))

Create the model and define the optimization method to use. In this case, learning works much better if we gradually
decrease the learning rate. We use an ExponentialDecay to multiply the learning rate by 0.9 after each epoch.

from deepchem.models.optimizers import Adam, ExponentialDecay

max_length = max(len(s) for s in train_smiles)
batch_size = 100
batches_per_epoch = len(train_smiles)/batch_size
model = dc.models.SeqToSeq(tokens,
tokens,
max_length,
encoder_layers=2,
decoder_layers=2,
embedding_dimension=256,
model_dir='fingerprint',
batch_size=batch_size,
learning_rate=ExponentialDecay(0.001, 0.9, batches_per_epoch))

Let's train it! The input to fit_sequences() is a generator that produces input/output pairs. On a good GPU, this
should take a few hours or less.

def generate_sequences(epochs):
for i in range(epochs):
for s in train_smiles:
yield (s, s)

model.fit_sequences(generate_sequences(40))

Let's see how well it works as an autoencoder. We'll run the first 500 molecules from the validation set through it, and
see how many of them are exactly reproduced.

predicted = model.predict_from_sequences(valid_smiles[:500])
count = 0
for s,p in zip(valid_smiles[:500], predicted):
if ''.join(p) == s:
count += 1
print('reproduced', count, 'of 500 validation SMILES strings')

reproduced 161 of 500 validation SMILES strings

Now we'll trying using the encoder as a way to generate molecular fingerprints. We compute the embedding vectors for
all molecules in the training and validation datasets, and create new datasets that have those as their feature vectors.
The amount of data is small enough that we can just store everything in memory.

import numpy as np
train_embeddings = model.predict_embeddings(train_smiles)
train_embeddings_dataset = dc.data.NumpyDataset(train_embeddings,
train_dataset.y,
train_dataset.w.astype(np.float32),
train_dataset.ids)

valid_embeddings = model.predict_embeddings(valid_smiles)
valid_embeddings_dataset = dc.data.NumpyDataset(valid_embeddings,
valid_dataset.y,
valid_dataset.w.astype(np.float32),
valid_dataset.ids)

For classification, we'll use a simple fully connected network with one hidden layer.

classifier = dc.models.MultitaskClassifier(n_tasks=len(tasks),
n_features=256,
layer_sizes=[512])
classifier.fit(train_embeddings_dataset, nb_epoch=10)

0.0014195525646209716

Find out how well it worked. Compute the ROC AUC for the training and validation datasets.

metric = dc.metrics.Metric(dc.metrics.roc_auc_score, np.mean, mode="classification")

train_score = classifier.evaluate(train_embeddings_dataset, [metric], transformers)
valid_score = classifier.evaluate(valid_embeddings_dataset, [metric], transformers)
print('Training set ROC AUC:', train_score)
print('Validation set ROC AUC:', valid_score)

Training set ROC AUC: {'mean-roc_auc_score': 0.9598792603154332}

Validation set ROC AUC: {'mean-roc_auc_score': 0.7251350862464794}

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Synthetic Feasibility
Synthetic feasibility is a problem when running large scale enumerations. Often molecules that are enumerated are very
difficult to make and thus not worth inspection, even if their other chemical properties are good in silico. This tutorial
goes through how to train the ScScore model [1].

The idea of the model is to train on pairs of molecules where one molecule is "more complex" than the other. The neural
network then can make scores which attempt to keep this pairwise ordering of molecules. The final result is a model
which can give a relative complexity of a molecule.

The paper trains on every reaction in reaxys, declaring products more complex than reactions. Since this training set is
prohibitively expensive we will instead train on arbitrary molecules declaring one more complex if its SMILES string is
longer. In the real world you can use whatever measure of complexity makes sense for the project.

In this tutorial, we'll use the Tox21 dataset to train our simple synthetic feasibility model.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

Make The Datasets

Let's begin by loading some molecules to work with. We load Tox21, specifying splitter=None so everything will be
returned as a single dataset.

import deepchem as dc
tasks, datasets, transformers = dc.molnet.load_tox21(featurizer='Raw', splitter=None)
molecules = datasets[0].X

Because ScScore is trained on relative complexities, we want the X tensor in our dataset to have 3 dimensions
(sample_id, molecule_id, features) . The molecule_id dimension has size 2 because a sample is a pair of
molecules. The label is 1 if the first molecule is more complex than the second molecule. The function create_dataset
we introduce below pulls random pairs of SMILES strings out of a given list and ranks them according to this complexity
measure.

In the real world you could use purchase cost, or number of reaction steps required as your complexity score.

from rdkit import Chem

import random
from deepchem.feat import CircularFingerprint
import numpy as np

def create_dataset(fingerprints, smiles_lens, ds_size=100000):

"""
m1: list of np.Array
fingerprints for molecules
m2: list of int
length of a molecules SMILES string

returns:
dc.data.Dataset for input into ScScore Model

Dataset.X
shape is (sample_id, molecule_id, features)
Dataset.y
shape is (sample_id,)
values is 1 if the 0th index molecule is more complex
0 if the 1st index molecule is more complex
"""
X, y = [], []
all_data = list(zip(fingerprints, smiles_lens))
while len(y) < ds_size:
i1= random.randrange(0, len(smiles_lens))
i2= random.randrange(0, len(smiles_lens))
m1= all_data[i1]
m2= all_data[i2]
ifm1[1] == m2[1]:
continue
if m1[1] > m2[1]:
y.append(1.0)
else:
y.append(0.0)
X.append([m1[0], m2[0]])
return dc.data.NumpyDataset(np.array(X), np.expand_dims(np.array(y), axis=1))

With our complexity ranker in place we can now construct our dataset. Let's start by randomly splitting the list of
molecules into training and test sets.

molecule_ds = dc.data.NumpyDataset(np.array(molecules))
splitter = dc.splits.RandomSplitter()
train_mols, test_mols = splitter.train_test_split(molecule_ds)

We'll featurize all our molecules with the ECFP fingerprint with chirality (matching the source paper), and will then
construct our pairwise dataset using the function defined above. We are using Circular Fingerprint featurizer, and
defining parameters such as the fingerprint size n_features, fingerprint radius radius, and whether to consider chirality
chiral. The Circular Fingerprint is a popular type of molecular fingerprint that encodes the structural information of
molecules.

n_features = 1024
featurizer = dc.feat.CircularFingerprint(size=n_features, radius=2, chiral=True)
train_features = featurizer.featurize(train_mols.X)
train_smiles_len = [len(Chem.MolToSmiles(x)) for x in train_mols.X]
train_dataset = create_dataset(train_features, train_smiles_len)

Now that we have our dataset created, let's train a ScScoreModel on this dataset.

model = dc.models.ScScoreModel(n_features=n_features)
model.fit(train_dataset, nb_epoch=20)

0.03494557857513428

Model Performance
Lets evaluate how well the model does on our holdout molecules. The SaScores should track the length of SMILES
strings from never before seen molecules.

import matplotlib.pyplot as plt

%matplotlib inline

mol_scores = model.predict_mols(test_mols.X)
smiles_lengths = [len(Chem.MolToSmiles(x)) for x in test_mols.X]

Let's now plot the length of the smiles string of the molecule against the SaScore using matplotlib.

plt.figure(figsize=(20,16))
plt.scatter(smiles_lengths, mol_scores)
plt.xlim(0,80)
plt.xlabel("SMILES length")
plt.ylabel("ScScore")
plt.show()
As we can see the model generally tracks SMILES length. It has good enrichment between 8 and 30 characters and gets
both small and large SMILES strings extremes dead on.

Now you can train your own models on more meaningful metrics than SMILES length!

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Bibliography:
[1] https://pubs.acs.org/doi/abs/10.1021/acs.jcim.7b00622
Calculating Atomic Contributions for Molecules Based on a
Graph Convolutional QSAR Model
In an earlier tutorial we introduced the concept of model interpretability: understanding why a model produced the
result it did. In this tutorial we will learn about atomic contributions, a useful tool for interpreting models that operate on
molecules.

The idea is simple: remove a single atom from the molecule and see how the model's prediction changes. The "atomic
contribution" for an atom is defined as the difference in activity between the whole molecule, and the fragment
remaining after atom removal. It is a measure of how much that atom affects the prediction.

Contributions are also known as "attributions", "coloration", etc. in the literature. This is a model interpretation method
[1], analogous to Similarity maps [2] in the QSAR domain, or occlusion methods in other fields (image classification, etc).
Present implementation was used in [4].

Mariia Matveieva, Pavel Polishchuk. Institute of Molecular and Translational Medicine, Palacky University, Olomouc,
Czech Republic.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following installation commands. This will take about 5 minutes to
run to completion and install your environment. You can of course run this tutorial locally if you prefer. In that case,
don't run these cells since they will download and install Anaconda on your local machine.

!curl -Lo conda_installer.py https://raw.githubusercontent.com/deepchem/deepchem/master/scripts/colab_install.py

import conda_installer
conda_installer.install()
!/root/miniconda/bin/conda info -e

% Total % Received % Xferd Average Speed Time Time Time Current

Dload Upload Total Spent Left Speed
100 3457 100 3457 0 0 24692 0 --:--:-- --:--:-- --:--:-- 24692
add /root/miniconda/lib/python3.7/site-packages to PYTHONPATH
python version: 3.7.12
fetching installer from https://repo.continuum.io/miniconda/Miniconda3-latest-Linux-x86_64.sh
done
installing miniconda to /root/miniconda
done
installing openmm, pdbfixer
added conda-forge to channels
done
conda packages installation finished!
# conda environments:
#
base * /root/miniconda
!pip install --pre deepchem
import deepchem
deepchem.__version__
Collecting deepchem
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'2.6.0.dev'
A classification QSAR model for blood-brain barrier permeability
BBB permeability is the ability of compounds to enter the central nervous system. Here we use a dataset of relatively
small compounds which are transported by diffusion without any carriers. The property is defined as
log10(concentration in brain / concentration in blood). Compounds with a positive value (and 0) are labeled active, and
others are labeled inactive. After modelling we will identify atoms favorable and unfavorable for diffusion.

First let's create the dataset. The molecules are stored in an SDF file.

import os
import pandas as pd
import deepchem as dc
import numpy as np
from rdkit import Chem
from rdkit.Chem import AllChem
from rdkit.Chem import Draw, PyMol, rdFMCS
from rdkit.Chem.Draw import IPythonConsole
from rdkit import rdBase
from deepchem import metrics
from IPython.display import Image, display
from rdkit.Chem.Draw import SimilarityMaps
import tensorflow as tf

current_dir = os.path.dirname(os.path.realpath('__file__'))
dc.utils.download_url(
'https://raw.githubusercontent.com/deepchem/deepchem/master/examples/tutorials/assets/atomic_contributions_tutori
current_dir,
'logBB.sdf'
)
DATASET_FILE =os.path.join(current_dir, 'logBB.sdf')
# Create RDKit mol objects, since we will need them later.
mols = [m for m in Chem.SDMolSupplier(DATASET_FILE) if m is not None ]
loader = dc.data.SDFLoader(tasks=["logBB_class"],
featurizer=dc.feat.ConvMolFeaturizer(),
sanitize=True)
dataset = loader.create_dataset(DATASET_FILE, shard_size=2000)

Now let's build and train a GraphConvModel.

np.random.seed(2020)
tf.random.set_seed(2020)

m = dc.models.GraphConvModel(1, mode="classification", batch_normalize=False, batch_size=100)

m.fit(dataset, nb_epoch=10)

/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin

g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_14:0", shape=(331,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_po
ol_1/Reshape_13:0", shape=(331, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_pool_1/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_17:0", shape=(1646,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_16:0", shape=(1646, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_20:0", shape=(1359,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_19:0", shape=(1359, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_23:0", shape=(148,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_po
ol_1/Reshape_22:0", shape=(148, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_pool_1/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_11:0", shape=(331,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_co
nv_1/Reshape_10:0", shape=(331, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_conv_1/Cast:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a l
arge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_13:0", shape=(1646,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_12:0", shape=(1646, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_1:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_15:0", shape=(1359,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_14:0", shape=(1359, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_2:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_17:0", shape=(148,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_co
nv_1/Reshape_16:0", shape=(148, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_conv_1/Cast_3:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_19:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv
_1/Reshape_18:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_conv_1/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_21:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv
_1/Reshape_20:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_conv_1/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_23:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv
_1/Reshape_22:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_conv_1/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_25:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv
_1/Reshape_24:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_conv_1/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_27:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv
_1/Reshape_26:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_conv_1/Cast_8:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_29:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv
_1/Reshape_28:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_conv_1/Cast_9:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_14:0", shape=(331,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool
/Reshape_13:0", shape=(331, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_pool/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a large
amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_17:0", shape=(1646,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_16:0", shape=(1646, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_20:0", shape=(1359,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_19:0", shape=(1359, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_23:0", shape=(148,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool
/Reshape_22:0", shape=(148, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_pool/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a large
amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_14:0", shape=(334,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_po
ol_1/Reshape_13:0", shape=(334, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_pool_1/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_17:0", shape=(1838,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_16:0", shape=(1838, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_20:0", shape=(1458,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_19:0", shape=(1458, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_23:0", shape=(120,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_po
ol_1/Reshape_22:0", shape=(120, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_pool_1/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_11:0", shape=(334,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_co
nv_1/Reshape_10:0", shape=(334, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_conv_1/Cast:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a l
arge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_13:0", shape=(1838,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_12:0", shape=(1838, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_1:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_15:0", shape=(1458,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_14:0", shape=(1458, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_2:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_17:0", shape=(120,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_co
nv_1/Reshape_16:0", shape=(120, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model/graph_conv_1/Cast_3:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_14:0", shape=(334,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool
/Reshape_13:0", shape=(334, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_pool/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a large
amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_17:0", shape=(1838,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_16:0", shape=(1838, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_20:0", shape=(1458,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_19:0", shape=(1458, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_23:0", shape=(120,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool
/Reshape_22:0", shape=(120, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_mod
el/graph_pool/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a large
amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_14:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_13:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_17:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_16:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_20:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_19:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_11:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_10:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a
large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_13:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_12:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_1:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_15:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_14:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_2:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_14:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_13:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_17:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_16:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_20:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_19:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool_1/
Reshape_23:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_p
ool_1/Reshape_22:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_pool_1/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_conv_1/
Reshape_17:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_c
onv_1/Reshape_16:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model/graph_conv_1/Cast_3:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model/graph_pool/Re
shape_23:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model/graph_poo
l/Reshape_22:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras_m
odel/graph_pool/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume a lar
ge amount of memory.
"shape. This may consume a large amount of memory." % value)
0.5348201115926107

Let's load a test set and see how well it works.

current_dir = os.path.dirname(os.path.realpath('__file__'))
dc.utils.download_url(
'https://raw.githubusercontent.com/deepchem/deepchem/master/examples/tutorials/assets/atomic_contributions_tutori
current_dir,
'logBB_test_.sdf'
)
TEST_DATASET_FILE = os.path.join(current_dir, 'logBB_test_.sdf')
loader = dc.data.SDFLoader(tasks=["p_np"], sanitize=True,
featurizer=dc.feat.ConvMolFeaturizer())
test_dataset = loader.create_dataset(TEST_DATASET_FILE, shard_size=2000)
pred = m.predict(test_dataset)
pred = np.argmax(np.squeeze(pred),axis=1)
ba = metrics.balanced_accuracy_score(y_true=test_dataset.y, y_pred=pred)
print(ba)

0.7444444444444445

The balanced accuracy is high enough. Now let's proceed to model interpretation and estimate the contributions of
individual atoms to the prediction.

A fragment dataset
Now let's prepare a dataset of fragments based on the training set. (Any other unseen data set of interest can also be
used). These fragments will be used to evaluate the contributions of individual atoms.

For each molecule we will generate a list of ConvMol objects. Specifying per_atom_fragmentation=True tells it to
iterate over all heavy atoms and featurize a single-atom-depleted version of the molecule with each one removed.

loader = dc.data.SDFLoader(tasks=[],# dont need task (moreover, passing the task can lead to inconsitencies in data s
featurizer=dc.feat.ConvMolFeaturizer(per_atom_fragmentation=True),
sanitize=True)
frag_dataset = loader.create_dataset(DATASET_FILE, shard_size=5000)

/usr/local/lib/python3.7/dist-packages/numpy/core/_asarray.py:83: VisibleDeprecationWarning: Creating an ndarray

from ragged nested sequences (which is a list-or-tuple of lists-or-tuples-or ndarrays with different lengths or
shapes) is deprecated. If you meant to do this, you must specify 'dtype=object' when creating the ndarray
return array(a, dtype, copy=False, order=order)
/usr/local/lib/python3.7/dist-packages/deepchem/data/data_loader.py:885: VisibleDeprecationWarning: Creating an
ndarray from ragged nested sequences (which is a list-or-tuple of lists-or-tuples-or ndarrays with different len
gths or shapes) is deprecated. If you meant to do this, you must specify 'dtype=object' when creating the ndarra
y
return np.array(features), valid_inds

The dataset still has the same number of samples as the original training set, but each sample is now represented as a
list of ConvMol objects (one for each fragment) rather than a single ConvMol.

IMPORTANT: The order of fragments depends on the input format. If SDF, the fragment order is the same as the atom
order in corresponding mol blocks. If SMILES (i.e. csv with molecules represented as SMILES), then the order is given by
RDKit CanonicalRankAtoms

print(frag_dataset.X.shape)

(298,)

We really want to treat each fragment as a separate sample. We can use a FlatteningTransformer to flatten the
fragments lists.

tr = dc.trans.FlatteningTransformer(frag_dataset)
frag_dataset = tr.transform(frag_dataset)
print(frag_dataset.X.shape)

(5111,)

Predicting atomic contributions to activity

Now we will predict the activity for molecules and for their fragments. Then, for each fragment, we'll find the activity
difference: the change in activity when removing one atom.

Note: Here, in classification context, we use the probability output of the model as the activity. So the contribution is the
probability difference, i.e. "how much a given atom increases/decreases the probability of the molecule being active."

# whole molecules
pred = np.squeeze(m.predict(dataset))[:, 1] # probabilitiy of class 1
pred = pd.DataFrame(pred, index=dataset.ids, columns=["Molecule"]) # turn to dataframe for convinience

# fragments
pred_frags = np.squeeze(m.predict(frag_dataset))[:, 1]
pred_frags = pd.DataFrame(pred_frags, index=frag_dataset.ids, columns=["Fragment"])

We take the difference to find the atomic contributions.

# merge 2 dataframes by molecule names

df = pd.merge(pred_frags, pred, right_index=True, left_index=True)
# find contribs
df['Contrib'] = df["Molecule"] - df["Fragment"]

Fragment Molecule Contrib

C#CC1(O)CCC2C3C(C)CC4=C(CCC(=O)C4)C3CCC21C 0.756537 0.811550 0.055013

C#CC1(O)CCC2C3C(C)CC4=C(CCC(=O)C4)C3CCC21C 0.752759 0.811550 0.058791

C#CC1(O)CCC2C3C(C)CC4=C(CCC(=O)C4)C3CCC21C 0.747012 0.811550 0.064538

C#CC1(O)CCC2C3C(C)CC4=C(CCC(=O)C4)C3CCC21C 0.815878 0.811550 -0.004328

C#CC1(O)CCC2C3C(C)CC4=C(CCC(=O)C4)C3CCC21C 0.741805 0.811550 0.069745

... ... ... ...

c1cncc(C2CCCN2)c1 0.780473 0.813031 0.032559

c1cncc(C2CCCN2)c1 0.722649 0.813031 0.090383

c1cncc(C2CCCN2)c1 0.721607 0.813031 0.091425

c1cncc(C2CCCN2)c1 0.683299 0.813031 0.129732

c1cncc(C2CCCN2)c1 0.674451 0.813031 0.138581

5111 rows × 3 columns

We can use the SimilarityMaps feature of RDKit to visualize the results. Each atom is colored by how it affects activity.

def vis_contribs(mols, df, smi_or_sdf = "sdf"):

# input format of file, which was used to create dataset determines the order of atoms,
# so we take it into account for correct mapping!
maps = []
for mol in mols:
wt = {}
if smi_or_sdf == "smi":
for n,atom in enumerate(Chem.rdmolfiles.CanonicalRankAtoms(mol)):
wt[atom] = df.loc[mol.GetProp("_Name"),"Contrib"][n]
if smi_or_sdf == "sdf":
for n,atom in enumerate(range(mol.GetNumHeavyAtoms())):
wt[atom] = df.loc[Chem.MolToSmiles(mol),"Contrib"][n]
maps.append(SimilarityMaps.GetSimilarityMapFromWeights(mol,wt))
return maps

Let's look at some pictures:

np.random.seed(2000)
maps = vis_contribs(np.random.choice(np.array(mols),10), df)
We can see that aromatics or aliphatics have a positive impact on blood-brain barrier permeability, while polar or
charged heteroatoms have a negative influence. This is generally consistent with literature data.

A regression task
The example above used a classification model. The same techniques can also be used for regression models. Let's look
at a regression task, aquatic toxicity (towards the water organism T. pyriformis).

Toxicity is defined as log10(IGC50) (concentration that inhibits colony growth by 50%). Toxicophores for T. pyriformis
will be identified by atomic contributions.

All the above steps are the same: load data, featurize, build a model, create dataset of fragments, find contributions,
and visualize them.

Note: this time as it is regression, contributions will be in activity units, not probability.

# create RDKit mol objects, we will need them later

mols = [m for m in Chem.SDMolSupplier(DATASET_FILE) if m is not None ]
loader = dc.data.SDFLoader(tasks=["IGC50"],
featurizer=dc.feat.ConvMolFeaturizer(), sanitize=True)
dataset = loader.create_dataset(DATASET_FILE, shard_size=5000)

Create and train the model.

np.random.seed(2020)
tf.random.set_seed(2020)
m = dc.models.GraphConvModel(1, mode="regression", batch_normalize=False)
m.fit(dataset, nb_epoch=40)

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3/Reshape_14:0", shape=(291,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_3/Reshape_13:0", shape=(291, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_3/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
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3/Reshape_17:0", shape=(910,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_3/Reshape_16:0", shape=(910, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_3/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
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3/Reshape_20:0", shape=(663,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_3/Reshape_19:0", shape=(663, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_3/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
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3/Reshape_23:0", shape=(28,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph
_pool_3/Reshape_22:0", shape=(28, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model_1/graph_pool_3/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
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3/Reshape_11:0", shape=(291,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_conv_3/Reshape_10:0", shape=(291, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_conv_3/Cast:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
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3/Reshape_13:0", shape=(910,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_conv_3/Reshape_12:0", shape=(910, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_conv_3/Cast_1:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
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3/Reshape_15:0", shape=(663,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_conv_3/Reshape_14:0", shape=(663, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_conv_3/Cast_2:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
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_conv_3/Reshape_16:0", shape=(28, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model_1/graph_conv_3/Cast_3:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
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3/Reshape_19:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_
conv_3/Reshape_18:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model_1/graph_conv_3/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
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3/Reshape_21:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_
conv_3/Reshape_20:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model_1/graph_conv_3/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
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conv_3/Reshape_22:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model_1/graph_conv_3/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_25:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_
conv_3/Reshape_24:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model_1/graph_conv_3/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_27:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_
conv_3/Reshape_26:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model_1/graph_conv_3/Cast_8:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_29:0", shape=(0,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_
conv_3/Reshape_28:0", shape=(0, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_keras
_model_1/graph_conv_3/Cast_9:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consume
a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_14:0", shape=(291,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_2/Reshape_13:0", shape=(291, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_2/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_17:0", shape=(910,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_2/Reshape_16:0", shape=(910, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_2/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_20:0", shape=(663,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_2/Reshape_19:0", shape=(663, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_2/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_23:0", shape=(28,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph
_pool_2/Reshape_22:0", shape=(28, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model_1/graph_pool_2/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_14:0", shape=(307,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_3/Reshape_13:0", shape=(307, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_3/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_17:0", shape=(944,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_3/Reshape_16:0", shape=(944, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_3/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_20:0", shape=(693,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_3/Reshape_19:0", shape=(693, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_3/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_23:0", shape=(16,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph
_pool_3/Reshape_22:0", shape=(16, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model_1/graph_pool_3/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_11:0", shape=(307,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_conv_3/Reshape_10:0", shape=(307, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_conv_3/Cast:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_13:0", shape=(944,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_conv_3/Reshape_12:0", shape=(944, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_conv_3/Cast_1:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_15:0", shape=(693,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_conv_3/Reshape_14:0", shape=(693, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_conv_3/Cast_2:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_17:0", shape=(16,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph
_conv_3/Reshape_16:0", shape=(16, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model_1/graph_conv_3/Cast_3:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_14:0", shape=(307,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_2/Reshape_13:0", shape=(307, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_2/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_17:0", shape=(944,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_2/Reshape_16:0", shape=(944, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_2/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_20:0", shape=(693,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/grap
h_pool_2/Reshape_19:0", shape=(693, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_k
eras_model_1/graph_pool_2/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_23:0", shape=(16,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph
_pool_2/Reshape_22:0", shape=(16, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv_ker
as_model_1/graph_pool_2/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may consu
me a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_14:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_3/Reshape_13:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_3/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_17:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_3/Reshape_16:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_3/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_20:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_3/Reshape_19:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_3/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
3/Reshape_23:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_3/Reshape_22:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_3/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_11:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_conv_3/Reshape_10:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_conv_3/Cast:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may con
sume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_13:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_conv_3/Reshape_12:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_conv_3/Cast_1:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_15:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_conv_3/Reshape_14:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_conv_3/Cast_2:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_conv_
3/Reshape_17:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_conv_3/Reshape_16:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_conv_3/Cast_3:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_14:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_2/Reshape_13:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_2/Cast_4:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_17:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_2/Reshape_16:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_2/Cast_5:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_20:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_2/Reshape_19:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_2/Cast_6:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
/usr/local/lib/python3.7/dist-packages/tensorflow/python/framework/indexed_slices.py:450: UserWarning: Convertin
g sparse IndexedSlices(IndexedSlices(indices=Tensor("gradient_tape/private__graph_conv_keras_model_1/graph_pool_
2/Reshape_23:0", shape=(None,), dtype=int32), values=Tensor("gradient_tape/private__graph_conv_keras_model_1/gra
ph_pool_2/Reshape_22:0", shape=(None, 64), dtype=float32), dense_shape=Tensor("gradient_tape/private__graph_conv
_keras_model_1/graph_pool_2/Cast_7:0", shape=(2,), dtype=int32))) to a dense Tensor of unknown shape. This may c
onsume a large amount of memory.
"shape. This may consume a large amount of memory." % value)
0.12407124519348145

Load the test dataset and check the model's performance.

TEST_DATASET_FILE = os.path.join(current_dir, 'Tetrahymena_pyriformis_Test_set_OCHEM.sdf')

loader = dc.data.SDFLoader(tasks=["IGC50"], sanitize= True,
featurizer=dc.feat.ConvMolFeaturizer())
test_dataset = loader.create_dataset(TEST_DATASET_FILE, shard_size=2000)
pred = m.predict(test_dataset)
mse = metrics.mean_squared_error(y_true=test_dataset.y, y_pred=pred)
r2 = metrics.r2_score(y_true=test_dataset.y, y_pred=pred)
print(mse)
print(r2)

0.2381780323921622
0.784334539071699

Load the training set again, but this time set per_atom_fragmentation=True .

loader = dc.data.SDFLoader(tasks=[], # dont need any task

sanitize=True,
featurizer=dc.feat.ConvMolFeaturizer(per_atom_fragmentation=True))
frag_dataset = loader.create_dataset(DATASET_FILE, shard_size=5000)
tr = dc.trans.FlatteningTransformer(frag_dataset) # flatten dataset and add ids to each fragment
frag_dataset = tr.transform(frag_dataset)

/usr/local/lib/python3.7/dist-packages/numpy/core/_asarray.py:83: VisibleDeprecationWarning: Creating an ndarray

Compute the activity differences.

# whole molecules
pred = m.predict(dataset)
pred = pd.DataFrame(pred, index=dataset.ids, columns=["Molecule"]) # turn to dataframe for convenience
# fragments
pred_frags = m.predict(frag_dataset)
pred_frags = pd.DataFrame(pred_frags, index=frag_dataset.ids, columns=["Fragment"]) # turn to dataframe for convenie

# merge 2 dataframes by molecule names

df = pd.merge(pred_frags, pred, right_index=True, left_index=True)
# find contribs
df['Contrib'] = df["Molecule"] - df["Fragment"]

Lets take some molecules with moderate activity (not extremely active/inactive) and visualize the atomic contributions.

maps = vis_contribs([mol for mol in mols if float(mol.GetProp("IGC50"))>3 and float(mol.GetProp("IGC50"))<4][:10],

We can see that known toxicophores are in green, namely nitro-aromatics, halo-aromatics, long alkyl chains, and
aldehyde; while carboxylic groups, alcohols, and aminos are detoxyfying, as is consistent with literature [3]

Appendix
In this tutorial we operated on SDF files. However, if we use CSV files with SMILES as input, the order of the atoms in the
dataframe DOES NOT correspond to the original atom order. If we want to recover the original atom order for each
molecule (to have it in our main dataframe), we need to use RDKit's Chem.rdmolfiles.CanonicalRankAtoms. Here are
some utilities to do this.
We can add a column with atom ids (as in input molecules) and use the resulting dataframe for analysis with any other
software, outside the "python-rdkit-deepchem" environment.

def get_mapping(mols, mol_names):

"""perform mapping:
atom number original <-> atom number(position)
after ranking (both 1-based)"""
# mols - RDKit mols
# names - any seq of strings
# return list of nested lists: [[molecule, [atom , atom, ..], [...]]
assert(len(mols)==len(mol_names))
mapping = []
for m,n in zip(mols, mol_names):
atom_ids = [i+1 for i in list(Chem.rdmolfiles.CanonicalRankAtoms(m))]
mapping.append([n, atom_ids])
return mapping

def append_atomid_col(df, mapping):

# add column with CORRECT atom number(position)
for i in mapping:
df.loc[i[0],"AtomID"] = i[1]
return df

Bibliography:
1. Polishchuk, P., O. Tinkov, T. Khristova, L. Ognichenko, A. Kosinskaya, A. Varnek & V. Kuz’min (2016) Structural and
Physico-Chemical Interpretation (SPCI) of QSAR Models and Its Comparison with Matched Molecular Pair Analysis.
Journal of Chemical Information and Modeling, 56, 1455-1469.

2. Riniker, S. & G. Landrum (2013) Similarity maps - a visualization strategy for molecular fingerprints and machine-
learning methods. Journal of Cheminformatics, 5, 43.

3. M. Matveieva, M. T. D. Cronin, P. Polishchuk, Mol. Inf. 2019, 38, 1800084.

4. Matveieva, M., Polishchuk, P. Benchmarks for interpretation of QSAR models. J Cheminform 13, 41 (2021).
https://doi.org/10.1186/s13321-021-00519-x

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Interactive model evaluation with Trident Chemwidgets
In this tutorial we'll build on the Introduction to Graph Covolutions tutorial to show how you can use the Trident
Chemwidgets (TCW) package to interact with and test the model you've trained.

Evaluating models on new data, including corner cases, is a critical step toward model deployment. However,
generating new molecules to test in an interactive way is rarely straightforward. TCW provides several tools to help
subset larger datasets and draw new molecules to test against your models. You can find the full documentation for the
Trident Chemwidgets library here.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Installing the prerequisites

!pip install tensorflow deepchem trident-chemwidgets seaborn

For this tutorial, you'll need Trident Chemwidgets version 0.2.0 or greater. We can check the installed version with the
following command:

import trident_chemwidgets as tcw

print(tcw.__version__)

0.2.1

Throughout this tutorial, we'll use the convention tcw to call the classes from the Trident Chemwidgets package.

Exploring the data

We'll start out by loading the Tox21 dataset and extracting the predefined train, validation, and test splits.

import deepchem as dc

tasks, datasets, transformers = dc.molnet.load_tox21(featurizer='GraphConv')

train_dataset, valid_dataset, test_dataset = datasets

We can then use RDKit to calculate some additional features for each of the training examples. Specifically, we'll
compute the logP and molecular weight of each molecule and return this new data in a dataframe.

import rdkit.Chem as Chem

from rdkit.Chem.Crippen import MolLogP
from rdkit.Chem.Descriptors import MolWt
import pandas as pd

data = []

for dataset, split in zip(datasets, ['train', 'valid', 'test']):

for smiles in dataset.ids:
mol = Chem.MolFromSmiles(smiles)
logp = MolLogP(mol)
mwt = MolWt(mol)
data.append({
'smiles': smiles,
'logp': logp,
'mwt': mwt,
'split': split
})

mol_data = pd.DataFrame(data)

mol_data.head()

[15:36:55] WARNING: not removing hydrogen atom without neighbors

smiles logp mwt split

0 CC(O)(P(=O)(O)O)P(=O)(O)O -0.9922 206.027 train

1 CC(C)(C)OOC(C)(C)CCC(C)(C)OOC(C)(C)C 4.8172 290.444 train

2 OC[C@H](O)[C@@H](O)[C@H](O)CO -2.9463 152.146 train

3 CCCCCCCC(=O)[O-].CCCCCCCC(=O)[O-].[Zn+2] 2.1911 351.802 train

4 CC(C)COC(=O)C(C)C 1.8416 144.214 train

One-dimensional distributions
We can examine one-dimensional distributions using a histogram. Unlike histograms from static plotting libraries like
Matplotlib or Seaborn, the TCW Histogram provides interactive functionality. TCW enables subsetting of the data,
plotting chemical structures in a gallery next to the plot, and saving a reference to the subset portion of the dataframe.
Unfortunately, this interactivity comes at the price of portability, so we have included screenshots for this tutorial in
addition to providing the code to generate the interactive visuals. If you run this tutorial yourself (either locally or on
Colab), you'll be able to display and interact with full demo plots.

In the plot below, you can see the histogram of the molecular weight distribution from the combined dataset on the left.
If you click and drag within plot area in the live widget, you can subset a portion of the distribution for further
examination. The background of the selected portion will turn gray and the selected data points will be shown in teal
within the bars of the plot. The x axis of the Histogram widget is compatible with either numeric or date data types,
which makes it a convenient choice for splitting your ML datasets based on a property or the date the experimental data
were collected.

Histogram example
To generate an interactive example of the widget, run the next cell:

hist = tcw.Histogram(data=mol_data, smiles='smiles', x='mwt')

hist

Histogram(data={'points': [{'smiles': 'CC(O)(P(=O)(O)O)P(=O)(O)O', 'x': 206.027, 'index': 0}, {'smiles': 'CC(C…

If you select subset of the data by clicking and dragging, you can view the selected structures in the gallery to the right
by pressing the SHOW STRUCTURES button beneath the plot. You can extract this subset of the original dataframe by
pressing SAVE SELECTION and accessing the hist.selection property as shown in the next cell. This workflow is
convenient for applications like data splitting based on a single dimension.

hist.selection

smiles logp mwt split

Two- or three-dimensional distributions

In addition to histograms, TCW also has provides a class for scatter plots. The Scatter class is useful when comparing
two or three dimensions or your data. As of v0.2.0, TCW Scatter supports the use of the x and y axes as well as the color
of each point ( hue keyword) to represent either continuous or discrete variables. Just like in the Histogram example,
you can click and drag within the plot area to subset along the x and y axes. The Scatter widget also supports dates
along the x, y, and hue axes.

In the image below, we have selected a portion of dataset with large molecular weight values, but minimal training
examples (displayed points in orange), to demonstrate how the Scatter widget can be useful for outlier identification. In
addition to selection by bounding box, you can also hover over individual points to display a drawing of the underlying
structure.
Scatter example

To generate an interactive example of the widget, run the next cell:

scatter = tcw.Scatter(data=mol_data, smiles='smiles', x='mwt', y='logp', hue='split')

scatter

Scatter(data={'points': [{'smiles': 'CC(O)(P(=O)(O)O)P(=O)(O)O', 'x': 206.027, 'y': -0.9922000000000002, 'hue'…

If you select subset of the data by clicking and dragging, you can view the selected structures in the gallery to the right
by pressing the SHOW STRUCTURES button beneath the plot. You can extract this subset of the original dataframe by
pressing SAVE SELECTION and accessing the scatter.selection property as shown in the next cell.

scatter.selection

smiles logp mwt split

Training a GraphConvModel
Now that we've had a look at the training data, we can train a GraphConvModel to predict the 12 Tox21 classes. We'll
replicate the training procedure exactly from the Introduction to Graph Covolutions tutorial. We'll train for 50 epochs,
just as in the original tutorial.

# The next line filters tensorflow warnings relevant to memory consumption.

# To see these warnings, comment the next line.
import warnings; warnings.filterwarnings('ignore')

# Now we'll set the tensorflow seed to make sure the results of this notebook are reproducible
import tensorflow as tf; tf.random.set_seed(27)
n_tasks = len(tasks)
model = dc.models.GraphConvModel(n_tasks, mode='classification')
model.fit(train_dataset, nb_epoch=50)

2022-06-29 15:37:03.915828: I tensorflow/core/platform/cpu_feature_guard.cc:193] This TensorFlow binary is optim

ized with oneAPI Deep Neural Network Library (oneDNN) to use the following CPU instructions in performance-criti
cal operations: AVX2 FMA
To enable them in other operations, rebuild TensorFlow with the appropriate compiler flags.
0.2661594772338867

Now that we have a trained model, we can check AUROC values for the training and test datasets:

metric = dc.metrics.Metric(dc.metrics.roc_auc_score)
print(f'Training set score: {model.evaluate(train_dataset, [metric], transformers)["roc_auc_score"]:.2f}')
print(f'Test set score: {model.evaluate(test_dataset, [metric], transformers)["roc_auc_score"]:.2f}')

Training set score: 0.97

Test set score: 0.68

Just as in the original tutorial, we see that the model performs reasonably well on the predefined train/test splits. Now
we'll use this model to evaluate compounds that are outside the training distribution, just as we might in a real-world
drug discovery scenario.

Evaluating the model on new data

One of the challenging first steps toward deploying an ML model in production is evaluating it on new data. Here, new
data refers to both data outside the initial train/val/test distributions and also data that may not be already processed
for use with the model.

We can use the JSME widget provided by TCW to quickly test our model again some molecules of interest. We'll start
with a known therapeutic molecule: ibuprofen. We can see that ibuprofen is not included in any of the datasets that we
have evaluated our model against so far:

print(f"Ibuprofen structure in Tox21 dataset: {'CC(C)CC1=CC=C(C=C1)C(C)C(=O)O' in mol_data['smiles']}")

Ibuprofen structure in Tox21 dataset: False

To simulate a drug discovery application, let's say you're a chemist tasked with identifying potential new therapeutics
derived from ibuprofen. Ideally, the molecules you test would have limited toxicity. You've just developed the model
above to predict the tox outcomes from Tox21 data and now you want to use it to do some first-pass screening of your
derivatives. The standard workflow for a task like this might include drawing the molecules in a program like ChemDraw,
exporting to SMILES format, importing into the notebook, then prepping the data and running it through your model.

With TCW, we can shortcut the first few steps of that workflow by using the JSME widget to draw molecules and convert
to SMILES directly in the notebook. We can even use the base_smiles argument to specify a base molecular structure,
which is great for generating derivatives. Here we'll set the base_smiles value to 'CC(C)CC1=CC=C(C=C1)C(C)C(=O)O' ,
the SMILES string for ibuprofen. Below is a screenshot using JSME to generate a few derivative molecules to test against
our toxicity model.
JSME example

To generate your own set of derivatives, run the cell below. To add a SMILES string to the saved set, click the ADD TO
SMILES LIST button below the interface. If you want to regenerate the original base molecule, in this case ibuprofen,
click the RESET TO BASE SMILES button below the interface. By using this button, it's easy to generate distinct
derivatives from a shared starting structure. Go ahead and create some ibuprofen derivatives to test against the tox
model:

jsme = tcw.JSME(base_smiles='CC(C)CC1=CC=C(C=C1)C(C)C(=O)O')
jsme

JSME(base_smiles='CC(C)CC1=CC=C(C=C1)C(C)C(=O)O')

You can access the smiles using the jsme.smiles property. This call will return a list of the SMILES strings that have
been added to the SMILES list of the widget (the ones shown in the molecule gallery to the right of the JSME interface).

print(jsme.smiles)

[]

To ensure the rest of this notebook runs correctly, the following cell sets the new test SMILES set to the ones from the
screenshot above in the case that you have not defined your own set using the widget. Otherwise, it will use the
molecules you have drawn.

# This cell will provide a preset list of SMILES strings in case you did not create your own.
if len(jsme.smiles) > 1:
drawn_smiles = jsme.smiles
else:
drawn_smiles = [
'CC(C)Cc1ccc(C(C)C(=O)O)cc1',
'CC(C)C(S)c1ccc(C(C)C(=O)O)cc1',
'CCSC(c1ccc(C(C)C(=O)O)cc1)C(C)CC',
'CCSC(c1ccc(C(C)C(=O)O)cc1)C(C)C(=O)O',
'CC(C(=O)O)c1ccc(C(S)C(C)C(=O)O)cc1'
]

Next we have to create a dataset that is compatible with our model to test these new molecules.

featurizer = dc.feat.ConvMolFeaturizer()
loader = dc.data.InMemoryLoader(tasks=list(train_dataset.tasks), featurizer=featurizer)
dataset = loader.create_dataset(drawn_smiles, shard_size=1)

Finally, we can generate our predictions of positive results here and plot them.

predictions = model.predict(dataset, transformers)[:, :, 1]

import seaborn as sns

sns.heatmap(predictions, vmin=0, vmax=1)

<AxesSubplot:>

Now we can get the predicted most toxic compound/assay result for further inspection. Below we extract the highest
predicted positive hit (most toxic) and display the assay name, SMILES string, and an image of the structure.

import numpy as np

mol_idx, assay_idx = np.unravel_index(predictions.argmax(), predictions.shape)

smiles = drawn_smiles[mol_idx]

print(f'Most toxic result (predicted): {train_dataset.tasks[assay_idx]}, {smiles}')

mol = Chem.MolFromSmiles(smiles)
mol

Most toxic result (predicted): NR-ER, CC(C)Cc1ccc(C(C)C(=O)O)cc1

Interpreting the model's predictions

Often predictions alone are insufficient to decide whether to move forward with costly experiments. We might also want
some metric or metrics that allow us to interpret the model's output.

Building on the tutorial Calculating Atomic Contributions for Molecules Based on a Graph Convolutional QSAR Model, we
can calculate the relative contribution of each atom in a molecule to the predicted output value. This attribution
strategy enables us to determine whether the molecular features that a chemist may identify as important and those
most affecting the predictions are in alignment. If the chemist's interpretation and the model's interpretation metrics
are consistent, that may indicate that the model is a good fit for the task at hand. However, the inverse is not
necessarily true either. A model may have the capacity to make accurate predictions that a trained chemist cannot fully
understand. This is just one tool in a machine learning practitioner's toolbox.

We'll start by using the built-in per_atom_fragmentation argument for the ConvMolFeaturizer . This will generate a
list of ConvMol objects that have each had a single atom removed.

featurizer = dc.feat.ConvMolFeaturizer(per_atom_fragmentation=True)
mol_list = featurizer(smiles)
loader = dc.data.InMemoryLoader(tasks=list(train_dataset.tasks),
featurizer=dc.feat.DummyFeaturizer())
dataset = loader.create_dataset(mol_list[0], shard_size=1)

We can then run these predictions through the model and retrieve the predicted values for the molecule and assay
specified in the last section.

full_molecule_prediction = predictions[mol_idx, assay_idx]

fragment_predictions = model.predict(dataset, transformers)[:, assay_idx, 0]
contributions = pd.DataFrame({
'Change in predicted toxicity':
(full_molecule_prediction - fragment_predictions).round(3)
})

We can use the InteractiveMolecule widget from TCW to superimpose the contribution scores on the molecule itself,
allowing us to easily asses the relative importance of each atom to the final prediction. If you click on one of the atoms,
you can retrieve the contribution data in a card shown to the right of the structure. In this panel you can also select a
variable by which to color the atoms in the plot.

InteractiveMolecule example

You can generate the interactive widget by running the cell below.

tcw.InteractiveMolecule(smiles, data = contributions)

InteractiveMolecule(data=[{'Change in predicted toxicity': 0.5529999732971191}, {'Change in predicted toxicity…

Wrapping up
In this tutorial, we learned how to incorporate Trident Chemwidgets into your DeepChem-based ML workflow. While TCW
was built with molecular ML workflows in mind, the library also works well for general cheminformatics notebooks as
well.

Star Trident Chemwidgets on GitHub

If you ﬁnd the Trident Chemwidgets package helpful please give it a ⭐ on GitHub. Starring the project helps it grow and
find new audiences.

Congratulations! Time to join the Community!

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build.

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sciences. Join the conversation!
Tutorial: ChemBERTa: Large-Scale Self-Supervised
Pretraining for Molecular Property Prediction using a
Smiles Tokenization Strategy

By Seyone Chithrananda (Twitter)

Deep learning for chemistry and materials science remains a novel field with lots of potiential. However, the popularity
of transfer learning based methods in areas such as natural language processing (NLP) and computer vision have not
yet been effectively developed in computational chemistry + machine learning. Using HuggingFace's suite of models
and the ByteLevel tokenizer, we are able to train a large-transformer model, RoBERTa, on a large corpus of 10,000,000
SMILES strings from a commonly known benchmark chemistry dataset, PubChem.

Training RoBERTa over 10 epochs, the model achieves a pretty good loss of 0.198, and may likely continue to converge
if trained for a larger number of epochs. The model can predict masked/corrupted tokens within a SMILES
sequence/molecule, allowing for variants of a molecule within discoverable chemical space to be predicted.

By applying the representations of functional groups and atoms learned by the model, we can try to tackle problems of
toxicity, solubility, drug-likeness, and synthesis accessibility on smaller datasets using the learned representations as
features for graph convolution and attention models on the graph structure of molecules, as well as fine-tuning of BERT.
Finally, we propose the use of attention visualization as a helpful tool for chemistry practitioners and students to quickly
identify important substructures in various chemical properties.

Additionally, visualization of the attention mechanism have been seen through previous research as incredibly valuable
towards chemical reaction classification. The applications of open-sourcing large-scale transformer models such as
RoBERTa with HuggingFace may allow for the acceleration of these individual research directions.

A link to a repository which includes the training, uploading and evaluation notebook (with sample predictions on
compounds such as Remdesivir) can be found here. All of the notebooks can be copied into a new Colab runtime for
easy execution. This repository will be updated with new features, such as attention visualization, easier benchmarking
infrastructure, and more. The work behind this tutorial has been published on Arxiv, and was accepted for a poster
presentation at NeurIPS 2020's ML for Molecules Workshop.

For the sake of this tutorial, we'll be fine-tuning a pre-trained ChemBERTa on a small-scale molecule dataset, Clintox, to
show the potiential and effectiveness of HuggingFace's NLP-based transfer learning applied to computational chemistry.
Output for some cells are purposely cleared for readability, so do not worry if some output messages for your cells
differ!

In short, there are three major components we'll be going over in this notebook.

1. Masked token inference predictions on SMILES strings

2. Attention visualizaiton of the PubChem-10M model
3. Fine-tuninhg BPE-ChemBERTa and Smiles-Tokenizer ChemBERTa model's on the CLintox toxicity dataset.

Don't worry if you aren't familiar with some of these terms. We will explain them later in the tutorial!

If you're looking to dive deeper, check out the poster here.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!curl -Lo conda_installer.py https://raw.githubusercontent.com/deepchem/deepchem/master/scripts/colab_install.py

import conda_installer
conda_installer.install()
!/root/miniconda/bin/conda info -e

% Total % Received % Xferd Average Speed Time Time Time Current

Dload Upload Total Spent Left Speed
100 3501 100 3501 0 0 16995 0 --:--:-- --:--:-- --:--:-- 16995
add /root/miniconda/lib/python3.7/site-packages to PYTHONPATH
python version: 3.7.10
remove current miniconda
fetching installer from https://repo.continuum.io/miniconda/Miniconda3-latest-Linux-x86_64.sh
done
installing miniconda to /root/miniconda
done
installing rdkit, openmm, pdbfixer
added omnia to channels
added conda-forge to channels
done
conda packages installation finished!
# conda environments:
#
base * /root/miniconda

!pip install --pre deepchem

import deepchem
deepchem.__version__

Requirement already satisfied: deepchem in /usr/local/lib/python3.7/dist-packages (2.5.0)

Requirement already satisfied: pandas in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.1.5)
Requirement already satisfied: scipy in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.4.1)
Requirement already satisfied: scikit-learn in /usr/local/lib/python3.7/dist-packages (from deepchem) (0.22.2.po
st1)
Requirement already satisfied: numpy in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.19.5)
Requirement already satisfied: joblib in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.0.1)
Requirement already satisfied: python-dateutil>=2.7.3 in /usr/local/lib/python3.7/dist-packages (from pandas->de
epchem) (2.8.1)
Requirement already satisfied: pytz>=2017.2 in /usr/local/lib/python3.7/dist-packages (from pandas->deepchem) (2
018.9)
Requirement already satisfied: six>=1.5 in /usr/local/lib/python3.7/dist-packages (from python-dateutil>=2.7.3->
pandas->deepchem) (1.15.0)
wandb: WARNING W&B installed but not logged in. Run `wandb login` or set the WANDB_API_KEY env variable.
wandb: WARNING W&B installed but not logged in. Run `wandb login` or set the WANDB_API_KEY env variable.
'2.5.0'

from rdkit import Chem

We want to install NVIDIA's Apex tool, for the training pipeline used by simple-transformers and Weights and Biases.
This package enables us to use 16-bit training, mixed precision, and distributed training without any changes to our
code. Generally GPUs are good at doing 32-bit(single precision) math, not at 16-bit(half) nor 64-bit(double precision).
Therefore traditionally deep learning model trainings are done in 32-bit. By switching to 16-bit, we’ll be using half the
memory and theoretically less computation at the expense of the available number range and precision. However, pure
16-bit training creates a lot of problems for us (imprecise weight updates, gradient underflow and overflow). Mixed
precision training, with Apex, alleviates these problems.

We will be installing simple-transformers , a library which builds ontop of HuggingFace's transformers package
specifically for fine-tuning ChemBERTa.

!git clone https://github.com/NVIDIA/apex

!cd /content/apex
!pip install -v --no-cache-dir /content/apex
!pip install transformers
!pip install simpletransformers
!pip install wandb
!cd ..

import sys
!test -d bertviz_repo && echo "FYI: bertviz_repo directory already exists, to pull latest version uncomment this line
# !rm -r bertviz_repo # Uncomment if you need a clean pull from repo
!test -d bertviz_repo || git clone https://github.com/jessevig/bertviz bertviz_repo
if not 'bertviz_repo' in sys.path:
sys.path += ['bertviz_repo']
!pip install regex

FYI: bertviz_repo directory already exists, to pull latest version uncomment this line: !rm -r bertviz_repo
Requirement already satisfied: regex in /usr/local/lib/python3.7/dist-packages (2019.12.20)
We're going to clone an auxillary repository, bert-loves-chemistry, which will enable us to use the MolNet dataloader for
ChemBERTa, which automatically generates scaffold splits on any MoleculeNet dataset!

!git clone https://github.com/seyonechithrananda/bert-loves-chemistry.git

fatal: destination path 'bert-loves-chemistry' already exists and is not an empty directory.

!nvidia-smi

Thu Mar 18 14:48:19 2021

+-----------------------------------------------------------------------------+
| Processes: |
| GPU GI CI PID Type Process name GPU Memory |
| ID ID Usage |
|=============================================================================|
| No running processes found |
+-----------------------------------------------------------------------------+

Now, to ensure our model demonstrates an understanding of chemical syntax and molecular structure, we'll be testing it
on predicting a masked token/character within the SMILES molecule for benzene.

# Test if NVIDIA apex training tool works

from apex import amp

What is a tokenizer?
A tokenizer is in charge of preparing the inputs for a natural language processing model. For many scientific
applications, it is possible to treat inputs as “words”/”sentences” and use NLP methods to make meaningful predictions.
For example, SMILES strings or DNA sequences have grammatical structure and can be usefully modeled with NLP
techniques. DeepChem provides some scientifically relevant tokenizers for use in different applications. These
tokenizers are based on those from the Huggingface transformers library (which DeepChem tokenizers inherit from).

The base classes PreTrainedTokenizer and PreTrainedTokenizerFast in HuggingFace implements the common methods
for encoding string inputs in model inputs and instantiating/saving python tokenizers either from a local file or directory
or from a pretrained tokenizer provided by the library (downloaded from HuggingFace’s AWS S3 repository).

PreTrainedTokenizer (transformers.PreTrainedTokenizer)) thus implements the main methods for using all the
tokenizers:

Tokenizing (spliting strings in sub-word token strings), converting tokens strings to ids and back, and
encoding/decoding (i.e. tokenizing + convert to integers),

Adding new tokens to the vocabulary in a way that is independant of the underlying structure (BPE,
SentencePiece…),

Managing special tokens like mask, beginning-of-sentence, etc tokens (adding them, assigning them to attributes in
the tokenizer for easy access and making sure they are not split during tokenization)

The default tokenizer used by ChemBERTa, is a Byte-Pair-Encoder (BPE). It is a hybrid between character and word-level
representations, which allows for the handling of large vocabularies in natural language corpora. Motivated by the
intuition that rare and unknown words can often be decomposed into multiple known subwords, BPE finds the best word
segmentation by iteratively and greedily merging frequent pairs of characters.

First, lets load the model's Byte-Pair Encoding tokenizer, and model, and setup a Huggingface pipeline for masked
tokeni prediction.

from transformers import AutoModelForMaskedLM, AutoTokenizer, pipeline, RobertaModel, RobertaTokenizer

from bertviz import head_view

model = AutoModelForMaskedLM.from_pretrained("seyonec/PubChem10M_SMILES_BPE_450k")
tokenizer = AutoTokenizer.from_pretrained("seyonec/PubChem10M_SMILES_BPE_450k")

fill_mask = pipeline('fill-mask', model=model, tokenizer=tokenizer)

What is a transformer model?

Previously, we spoke about the attention mechanism in modern deep learning models. Attention is a concept that
helped improve the performance of neural machine translation applications. The Transformer is a model that uses
attention to boost the speed with which these models can be trained.

With the emergence of BERT by Google AI in 2018, transformers have quickly shot to the top of emerging deep learning
methods, outperforming Neural Machine Translation models such as seq2seq and recurrent neural networks at dozens
of tasks.

The biggest benefit, however, comes from how The Transformer lends itself to efficient pre-training. Using the same
pre-training procedure used by RoBERTa, a follow-up work of BERT, which masks 15% of the tokens, we mask 15% of
the tokens in each SMILES string and assign a maximum sequence length of 256 characters.

The model then learns to predict masked tokens consisting of atoms and functional groups, or specific groups of
atoms within molecules which have their own characteristic properties. Through this, the model learns the relevant
molecular context for transferable tasks, such as property prediction.

ChemBERTa employs a bidirectional training context to learn context-aware representations of the PubChem 10M
dataset, downloadable through MoleculeNet for self-supervised pre-training (link). Our variant of the BERT transformer
uses 12 attention heads and 6 layers, resulting in 72 distinct attention mechanisms.

The Transformer was proposed in the paper Attention is All You Need.

Now, to ensure our the ChemBERTa model demonstrates an understanding of chemical syntax and molecular structure,
we'll be testing it on predicting a masked token/character within the SMILES molecule for benzene. Using the
Huggingface pipeline we initialized earlier we can fetch a list of the model's predictions by confidence score:

smiles_mask = "C1=CC=CC<mask>C1"
smiles = "C1=CC=CC=C1"

masked_smi = fill_mask(smiles_mask)

for smi in masked_smi:

print(smi)

{'sequence': 'C1=CC=CC=C1', 'score': 0.9755934476852417, 'token': 33, 'token_str': '='}

{'sequence': 'C1=CC=CC#C1', 'score': 0.020923888310790062, 'token': 7, 'token_str': '#'}
{'sequence': 'C1=CC=CC1C1', 'score': 0.0007658962858840823, 'token': 21, 'token_str': '1'}
{'sequence': 'C1=CC=CC2C1', 'score': 0.0004129768058191985, 'token': 22, 'token_str': '2'}
{'sequence': 'C1=CC=CC=[C1', 'score': 0.00025319133419543505, 'token': 352, 'token_str': '=['}

Here, we get some interesting results. The final branch, C1=CC=CC=C1 , is a benzene ring. Since its a pretty common
molecule, the model is easily able to predict the final double carbon bond with a score of 0.98. Let's get a list of the top
5 predictions (including the target, Remdesivir), and visualize them (with a highlighted focus on the beginning of the
final benzene-like pattern). To visualize them, we'll be using the RDKit cheminoformatics package we installed earlier,
specifically the rdkit.chem.Draw module.

import torch
import rdkit
import rdkit.Chem as Chem
from rdkit.Chem import rdFMCS
from matplotlib import colors
from rdkit.Chem import Draw
from rdkit.Chem.Draw import MolToImage
from PIL import Image

def get_mol(smiles):
mol = Chem.MolFromSmiles(smiles)
if mol is None:
return None
Chem.Kekulize(mol)
return mol

def find_matches_one(mol,submol):
#find all matching atoms for each submol in submol_list in mol.
match_dict = {}
mols = [mol,submol] #pairwise search
res=rdFMCS.FindMCS(mols) #,ringMatchesRingOnly=True)
mcsp = Chem.MolFromSmarts(res.smartsString)
matches = mol.GetSubstructMatches(mcsp)
return matches

#Draw the molecule

def get_image(mol,atomset):
hcolor = colors.to_rgb('green')
if atomset is not None:
#highlight the atoms set while drawing the whole molecule.
img = MolToImage(mol, size=(600, 600),fitImage=True, highlightAtoms=atomset,highlightColor=hcolor)
else:
img = MolToImage(mol, size=(400, 400),fitImage=True)
return img

sequence = f"C1=CC=CC={tokenizer.mask_token}1"
substructure = "CC=CC"
image_list = []

input = tokenizer.encode(sequence, return_tensors="pt")

mask_token_index = torch.where(input == tokenizer.mask_token_id)[1]

token_logits = model(input)[0]
mask_token_logits = token_logits[0, mask_token_index, :]

top_5_tokens = torch.topk(mask_token_logits, 5, dim=1).indices[0].tolist()

for token in top_5_tokens:

smi = (sequence.replace(tokenizer.mask_token, tokenizer.decode([token])))
print (smi)
smi_mol = get_mol(smi)
substructure_mol = get_mol(substructure)
if smi_mol is None: # if the model's token prediction isn't chemically feasible
continue
Draw.MolToFile(smi_mol, smi+".png")
matches = find_matches_one(smi_mol, substructure_mol)
atomset = list(matches[0])
img = get_image(smi_mol, atomset)
img.format="PNG"
image_list.append(img)

C1=CC=CC=CC1
C1=CC=CC=CCC1
C1=CC=CC=CN1
C1=CC=CC=CCCC1
C1=CC=CC=CCO1

from IPython.display import Image

for img in image_list:

display(img)
As we can see above, 5 out of 5 of the model's MLM predictions are chemically valid. Overall, the model seems to
understand syntax with a pretty decent degree of certainity.

However, further training on a more specific dataset (say leads for a specific target) may generate a stronger chemical
transformer model. Let's now fine-tune our model on a dataset of our choice, ClinTox. You can run ChemBERTa on any
MoleculeNet dataset, but for the sake of convinience, we will use ClinTox as it is small and trains quickly.

What is attention?
Previously, recurrent models struggled with generating a fixed-length vector for large sequences, leading to
deteriorating performance as the length of an input sequence increased.

Attention is, to some extent, motivated by how we pay visual attention to different regions of our vision or how we
correlate words in a sentence. Human visual attention allows us to focus on a certain subregion with a higher focus
while perceiving the surrounding image in with a lower focus, and then adjust the focal point.

Similarly, we can explain the relationship between words in one sentence or close context. When we see “eating”, we
expect to read a food word very soon. The color term describes the food, but probably not as directly as “eating” does:

The attention mechanism extends on the encoder-decoder model, by taking in three values for a SMILES sequence: a
value vector (V), a query vector (Q) and a key vector (K).

Each vector is similar to a type of word embedding, specifically for determining the compatibility of neighbouring
tokens. From these vectors, a dot production attention is derived from the dot product of the query vector of one word,
and the key vector of the other.
A scaling factor of

is added to the dot product attention such that the value doesn't grow too large in respect to

, the dimension of the key. The softmax normalization function is applied to return a score between 0 to 1 for each
individual token:

[Math Processing Error]

Visualizing the Attention Mechanism in ChemBERTa using

BertViz
BertViz is a tool for visualizing attention in the Transformer model, supporting all models from the transformers library
(BERT, GPT-2, XLNet, RoBERTa, XLM, CTRL, etc.). It extends the Tensor2Tensor visualization tool by Llion Jones and the
transformers library from HuggingFace.

Using this tool, we can easily plug in ChemBERTa from the HuggingFace model hub and visualize the attention patterns
produced by one or more attention heads in a given transformer layer. This is known as the attention-head view.

Lets start by obtaining a Javascript object for d3.js and jquery to create interactive visualizations:

%%javascript
require.config({
paths: {
d3: '//cdnjs.cloudflare.com/ajax/libs/d3/3.4.8/d3.min',
jquery: '//ajax.googleapis.com/ajax/libs/jquery/2.0.0/jquery.min',
}
});

def call_html():
import IPython
display(IPython.core.display.HTML('''
<script src="/static/components/requirejs/require.js"></script>
<script>
requirejs.config({
paths: {
base: '/static/base',
"d3": "https://cdnjs.cloudflare.com/ajax/libs/d3/3.5.8/d3.min",
jquery: '//ajax.googleapis.com/ajax/libs/jquery/2.0.0/jquery.min',
},
});
</script>
'''))

Now, we create an instance of ChemBERTa, tokenize a set of SMILES strings, and compute the attention for each head in
the transformer. There are two available models hosted by DeepChem on HuggingFace's model hub, one being
seyonec/ChemBERTa-zinc-base-v1 which is the ChemBERTa model trained via masked lagnuage modelling (MLM) on
the ZINC100k dataset, and the other being seyonec/ChemBERTa-zinc250k-v1 , which is trained via MLM on the larger
ZINC250k dataset.

In the following example, we take two SMILES molecules from the ZINC database with nearly identical chemical
structure, the only difference being rooted in chiral specification (hence the additional ‘@‘ symbol). This is a feature of
molecules which indicates that there exists tetrahedral centres. ‘@' tells us whether the neighbours of a molecule
appear in a counter-clockwise order, whereas ‘@@‘ indicates that the neighbours are ordered in a clockwise direction.
The model should ideally refer to similar substructures in each SMILES string with a higher attention weightage.

Lets look at the first SMILES string: CCCCC[C@@H](Br)CC :

m = Chem.MolFromSmiles('CCCCC[C@@H](Br)CC')
fig = Draw.MolToMPL(m, size=(200, 200))
And the second SMILES string, CCCCC[C@H](Br)CC :

m = Chem.MolFromSmiles('CCCCC[C@H](Br)CC')
fig = Draw.MolToMPL(m, size=(200,200))

The visualization below shows the attention induced by a sample input SMILES. This view visualizes attention as lines
connecting the tokens being updated (left) with the tokens being attended to (right), following the design of the figures
above. Color intensity reflects the attention weight; weights close to one show as very dark lines, while weights close to
zero appear as faint lines or are not visible at all. The user may highlight a particular SMILES character to see the
attention from that token only. This visualization is called the attention-head view. It is based on the
excellent Tensor2Tensor visualization tool, and are all generated by the Bertviz library.

from transformers import RobertaModel, RobertaTokenizer

from bertviz import head_view

model_version = 'seyonec/PubChem10M_SMILES_BPE_450k'
model = RobertaModel.from_pretrained(model_version, output_attentions=True)
tokenizer = RobertaTokenizer.from_pretrained(model_version)

sentence_a = "CCCCC[C@@H](Br)CC"
sentence_b = "CCCCC[C@H](Br)CC"
inputs = tokenizer.encode_plus(sentence_a, sentence_b, return_tensors='pt', add_special_tokens=True)
input_ids = inputs['input_ids']
attention = model(input_ids)[-1]
input_id_list = input_ids[0].tolist() # Batch index 0
tokens = tokenizer.convert_ids_to_tokens(input_id_list)

call_html()

head_view(attention, tokens)

Layer:
Smiles-Tokenizer Attention by Head View

The visualization shows that attention is highest between words that don’t cross a boundary between the two SMILES
strings; the model seems to understand that it should relate tokens to other tokens in the same molecule in order to
best understand their context.

There are many other fascinating visualizations we can do, such as a neuron-by neuron analysis of attention or a model
overview that visualizes all of the heads at once:

Attention by Head View:

Model View:
Neuron-by-neuron view:
You can try out the ChemBERTa attention visualization demo's in more detail, with custom SMILES/SELFIES strings,
tokenizers, and more in the public library, here.

What is Transfer Learning, and how does ChemBERTa

utilize it?
Transfer learning is a research problem in machine learning that focuses on storing knowledge gained while
solving one problem and applying it to a different but related problem.

By pre-training directly on SMILES strings, and teaching ChemBERTa to recognize masked tokens in each string, the
model learns a strong molecular representation. We then can take this model, trained on a structural chemistry task,
and apply it to a suite of classification tasks in the MoleculeNet suite, from Tox21 to BBBP!

Fine-tuning ChemBERTa on a Small Mollecular Dataset

Our fine-tuning dataset, ClinTox, consists of qualitative data of drugs approved by the FDA and those that have failed
clinical trials for toxicity reasons.

The ClinTox dataset consists of 1478 binary labels for toxicity, using the SMILES representations for identifying
molecules. The computational models produced from the dataset could become decision-making tools for government
agencies in determining which drugs are of the greatest potential concern to human health. Additionally, these models
can act as drug screening tools in the drug discovery pipelines for toxicity.

Let's start by importing the MolNet dataloder from bert-loves-chemistry , before importing apex and transformers,
the tool which will allow us to import the ChemBERTA language model (LM) trained on PubChem-10M.

%cd /content/bert-loves-chemistry

/content/bert-loves-chemistry

!pwd

/content/bert-loves-chemistry

import os

import numpy as np
import pandas as pd

from typing import List

# import molnet loaders from deepchem
from deepchem.molnet import load_bbbp, load_clearance, load_clintox, load_delaney, load_hiv, load_qm7, load_tox21
from rdkit import Chem

# import MolNet dataloder from bert-loves-chemistry fork

from chemberta.utils.molnet_dataloader import load_molnet_dataset, write_molnet_dataset_for_chemprop

But why use custom Smiles-Tokenizer's over BPE?

In this tutorial, we will be comparing the BPE tokenization algorithm with a custom SmilesTokenizer based on a regex
pattern, which we have released as part of DeepChem. To compare tokenizers, we pretrained an identical model
tokenized using this novel tokenizer, on the PubChem-1M set. The pretrained model was evaluated on the BBBP and
Tox21 in the paper. We found that the SmilesTokenizer narrowly outperformed the BPE algorithm by ∆PRC-AUC =

Though this result suggests that a more semantically relevant tokenization may provide performance benefits, further
benchmarking on additional datasets is needed to validate this finding. In this tutorial, we aim to do so, by testing
this alternate model on the ClinTox dataset.

Let's fetch the Smiles Tokenizer's character per line vocabulary file, which can bve loaded from the DeepChem S3 data
bucket:

!wget https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/vocab.txt

--2021-03-18 14:48:45-- https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/vocab.txt

Resolving deepchemdata.s3-us-west-1.amazonaws.com (deepchemdata.s3-us-west-1.amazonaws.com)... 52.219.113.41
Connecting to deepchemdata.s3-us-west-1.amazonaws.com (deepchemdata.s3-us-west-1.amazonaws.com)|52.219.113.41|:4
43... connected.
HTTP request sent, awaiting response... 200 OK
Length: 3524 (3.4K) [text/plain]
Saving to: ‘vocab.txt’

vocab.txt 100%[===================>] 3.44K --.-KB/s in 0s

2021-03-18 14:48:46 (62.2 MB/s) - ‘vocab.txt’ saved [3524/3524]

Lets use the MolNet dataloader to generate scaffold splits from the ClinTox dataset.

tasks, (train_df, valid_df, test_df), transformers = load_molnet_dataset("clintox", tasks_wanted=None)

'split' is deprecated. Use 'splitter' instead.
Failed to featurize datapoint 7, None. Appending empty array
Exception message: Python argument types in
rdkit.Chem.rdmolfiles.CanonicalRankAtoms(NoneType)
did not match C++ signature:
CanonicalRankAtoms(RDKit::ROMol mol, bool breakTies=True, bool includeChirality=True, bool includeIsotopes=T
rue)
Failed to featurize datapoint 302, None. Appending empty array
Exception message: Python argument types in
rdkit.Chem.rdmolfiles.CanonicalRankAtoms(NoneType)
did not match C++ signature:
CanonicalRankAtoms(RDKit::ROMol mol, bool breakTies=True, bool includeChirality=True, bool includeIsotopes=T
rue)
Failed to featurize datapoint 983, None. Appending empty array
Exception message: Python argument types in
rdkit.Chem.rdmolfiles.CanonicalRankAtoms(NoneType)
did not match C++ signature:
CanonicalRankAtoms(RDKit::ROMol mol, bool breakTies=True, bool includeChirality=True, bool includeIsotopes=T
rue)
Failed to featurize datapoint 984, None. Appending empty array
Exception message: Python argument types in
rdkit.Chem.rdmolfiles.CanonicalRankAtoms(NoneType)
did not match C++ signature:
CanonicalRankAtoms(RDKit::ROMol mol, bool breakTies=True, bool includeChirality=True, bool includeIsotopes=T
rue)
Failed to featurize datapoint 1219, None. Appending empty array
Exception message: Python argument types in
rdkit.Chem.rdmolfiles.CanonicalRankAtoms(NoneType)
did not match C++ signature:
CanonicalRankAtoms(RDKit::ROMol mol, bool breakTies=True, bool includeChirality=True, bool includeIsotopes=T
rue)
Failed to featurize datapoint 1220, None. Appending empty array
Exception message: Python argument types in
rdkit.Chem.rdmolfiles.CanonicalRankAtoms(NoneType)
did not match C++ signature:
CanonicalRankAtoms(RDKit::ROMol mol, bool breakTies=True, bool includeChirality=True, bool includeIsotopes=T
rue)
/usr/local/lib/python3.7/dist-packages/numpy/core/_asarray.py:83: VisibleDeprecationWarning: Creating an ndarray
from ragged nested sequences (which is a list-or-tuple of lists-or-tuples-or ndarrays with different lengths or
shapes) is deprecated. If you meant to do this, you must specify 'dtype=object' when creating the ndarray
return array(a, dtype, copy=False, order=order)
Using tasks ['CT_TOX'] from available tasks for clintox: ['FDA_APPROVED', 'CT_TOX']

If you're only running the toxicity prediction portion of this tutorial, make sure you install transformers here. If you've
ran all the cells before, you can ignore this install as we've already done pip install transformers before.

!pip install transformers

Requirement already satisfied: transformers in /usr/local/lib/python3.7/dist-packages (4.4.1)

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ges (from transformers) (3.7.2)
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2019.12.20)
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)
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hon_version < "3.8"->transformers) (3.4.1)
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formers) (3.0.4)
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rs) (2.10)
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(from requests->transformers) (1.24.3)
Requirement already satisfied: certifi>=2017.4.17 in /usr/local/lib/python3.7/dist-packages (from requests->tran
sformers) (2020.12.5)
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7.1.2)
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(1.0.1)
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formers) (2.4.7)
train_df

text labels

0 CC(C)C[C@H](NC(=O)CNC(=O)c1cc(Cl)ccc1Cl)B(O)O 0

1 O=C(NCC(O)CO)c1c(I)c(C(=O)NCC(O)CO)c(I)c(N(CCO... 1

2 Clc1cc(Cl)c(OCC#CI)cc1Cl 1

3 N#Cc1cc(NC(=O)C(=O)[O-])c(Cl)c(NC(=O)C(=O)[O-])c1 1

4 NS(=O)(=O)c1cc(Cl)c(Cl)c(S(N)(=O)=O)c1 1

... ... ...

1177 CC(C[NH2+]C1CCCCC1)OC(=O)c1ccccc1 1

1178 CC(C(=O)[O-])c1ccc(C(=O)c2cccs2)cc1 1

1179 CC(c1cc2ccccc2s1)N(O)C(N)=O 1

1180 CC(O)C(CO)NC(=O)C1CSSCC(NC(=O)C([NH3+])Cc2cccc... 1

1181 CC(C)OC(=O)CCC/C=C\C[C@H]1[C@@H](O)C[C@@H](O)[... 1

1182 rows × 2 columns

valid_df

text labels

0 CC(C)OC(=O)CCC/C=C\C[C@H]1[C@@H](O)C[C@@H](O)[... 1

1 CC(C)Nc1cccnc1N1CCN(C(=O)c2cc3cc(NS(C)(=O)=O)c... 1

2 CC(C)n1c(/C=C/[C@H](O)C[C@H](O)CC(=O)[O-])c(-c... 1

3 CC(C)COCC(CN(Cc1ccccc1)c1ccccc1)[NH+]1CCCC1 1

4 CSCC[C@H](NC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)... 1

... ... ...

143 C[C@H](OC(=O)c1ccccc1)C1=CCC23OCC[NH+](C)CC12C... 1

144 C[C@@H](c1ncncc1F)[C@](O)(Cn1cncn1)c1ccc(F)cc1F 1

145 CC(C)C[C@@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H]... 1

146 C[C@H](O)[C@H](O)[C@H]1CNc2[nH]c(N)nc(=O)c2N1 1

147 C[NH+]1C[C@H](C(=O)N[C@]2(C)O[C@@]3(O)[C@@H]4C... 1

148 rows × 2 columns

test_df

text labels

0 C[NH+]1C[C@H](C(=O)N[C@]2(C)O[C@@]3(O)[C@@H]4C... 1

1 C[C@]1(Cn2ccnn2)[C@H](C(=O)[O-])N2C(=O)C[C@H]2... 1

2 C[NH+]1CCC[C@@H]1CCO[C@](C)(c1ccccc1)c1ccc(Cl)cc1 1

3 Nc1nc(NC2CC2)c2ncn([C@H]3C=C[C@@H](CO)C3)c2n1 1

4 OC[C@H]1O[C@@H](n2cnc3c2NC=[NH+]C[C@H]3O)C[C@@... 1

... ... ...

143 O=C1O[C@H]([C@@H](O)CO)C([O-])=C1O 1

144 C#CCC(Cc1cnc2nc(N)nc(N)c2n1)c1ccc(C(=O)N[C@@H]... 1

145 C#CC[NH2+][C@@H]1CCc2ccccc21 1

146 [H]/[NH+]=C(\N)c1ccc(OCCCCCOc2ccc(/C(N)=[NH+]/... 1

147 [H]/[NH+]=C(\N)C1=CC(=O)/C(=C\C=c2ccc(=C(N)[NH... 1

148 rows × 2 columns

From here, lets set up a logger to record if any issues occur, and notify us if there are any problems with the arguments
we've set for the model.
from simpletransformers.classification import ClassificationModel
import logging
logging.basicConfig(level=logging.INFO)
transformers_logger = logging.getLogger("transformers")
transformers_logger.setLevel(logging.WARNING)

Now, using simple-transformer , let's load the pre-trained model from HuggingFace's useful model-hub. We'll set the
number of epochs to 10 in the arguments, but you can train for longer, and pass early-stopping as an argument to
prevent overfitting. Also make sure that auto_weights is set to True to do automatic weight balancing, as we are
dealing with imbalanced toxicity datasets.

from simpletransformers.classification import ClassificationModel, ClassificationArgs

model = ClassificationModel('roberta', 'seyonec/PubChem10M_SMILES_BPE_396_250', args={'evaluate_each_epoch': True,

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Some weights of the model checkpoint at seyonec/PubChem10M_SMILES_BPE_396_250 were not used when initializing Ro
bertaForSequenceClassification: ['lm_head.bias', 'lm_head.dense.weight', 'lm_head.dense.bias', 'lm_head.layer_no
rm.weight', 'lm_head.layer_norm.bias', 'lm_head.decoder.weight', 'lm_head.decoder.bias']
- This IS expected if you are initializing RobertaForSequenceClassification from the checkpoint of a model train
ed on another task or with another architecture (e.g. initializing a BertForSequenceClassification model from a
BertForPreTraining model).
- This IS NOT expected if you are initializing RobertaForSequenceClassification from the checkpoint of a model t
hat you expect to be exactly identical (initializing a BertForSequenceClassification model from a BertForSequenc
eClassification model).
Some weights of RobertaForSequenceClassification were not initialized from the model checkpoint at seyonec/PubCh
em10M_SMILES_BPE_396_250 and are newly initialized: ['classifier.dense.weight', 'classifier.dense.bias', 'classi
fier.out_proj.weight', 'classifier.out_proj.bias']
You should probably TRAIN this model on a down-stream task to be able to use it for predictions and inference.
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print(model.tokenizer)

PreTrainedTokenizer(name_or_path='seyonec/PubChem10M_SMILES_BPE_396_250', vocab_size=7924, model_max_len=1000000

000000000019884624838656, is_fast=False, padding_side='right', special_tokens={'bos_token': AddedToken("<s>", rs
trip=False, lstrip=False, single_word=False, normalized=True), 'eos_token': AddedToken("</s>", rstrip=False, lst
rip=False, single_word=False, normalized=True), 'unk_token': AddedToken("<unk>", rstrip=False, lstrip=False, sin
gle_word=False, normalized=True), 'sep_token': AddedToken("</s>", rstrip=False, lstrip=False, single_word=False,
normalized=True), 'pad_token': AddedToken("<pad>", rstrip=False, lstrip=False, single_word=False, normalized=Tru
e), 'cls_token': AddedToken("<s>", rstrip=False, lstrip=False, single_word=False, normalized=True), 'mask_token'
: AddedToken("<mask>", rstrip=False, lstrip=True, single_word=False, normalized=True)})

# check if our train and evaluation dataframes are setup properly. There should only be two columns for the SMILES st
print("Train Dataset: {}".format(train_df.shape))
print("Eval Dataset: {}".format(valid_df.shape))
print("TEST Dataset: {}".format(test_df.shape))

Train Dataset: (1182, 2)

Eval Dataset: (148, 2)
TEST Dataset: (148, 2)

Now that we've set everything up, lets get to the fun part: training the model! We use Weights and Biases, which is
optional (simply remove wandb_project from the list of args ). Its a really useful tool for monitering the model's
training results (such as accuracy, learning rate and loss), alongside custom visualizations of attention and gradients.

When you run this cell, Weights and Biases will ask for an account, which you can setup through a Github account,
giving you an authorization API key which you can paste into the output of the cell. Again, this is completely optional
and it can be removed from the list of arguments.

!wandb login

wandb: You can find your API key in your browser here: https://wandb.ai/authorize
wandb: Paste an API key from your profile and hit enter:
wandb: Appending key for api.wandb.ai to your netrc file: /root/.netrc

Finally, the moment we've been waiting for! Let's train the model on the train scaffold set of ClinTox, and monitor our
runs using W&B. We will evaluate the performance of our model each epoch using the validation set.

# Create directory to store model weights (change path accordingly to where you want!)
!mkdir BPE_PubChem_10M_ClinTox_run

# Train the model

model.train_model(train_df, eval_df=valid_df, output_dir='/content/BPE_PubChem_10M_ClinTox_run', args={'wandb_project

INFO:simpletransformers.classification.classification_utils: Converting to features started. Cache is not used.

0%| | 0/2 [00:00<?, ?it/s]
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rain_roberta_128_2_1182
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INFO:simpletransformers.classification.classification_model: Initializing WandB run for training.
wandb: Currently logged in as: seyonec (use `wandb login --relogin` to force relogin)
Tracking run with wandb version 0.10.22
Syncing run snowy-firefly-250 to Weights & Biases (Documentation).
Project page: https://wandb.ai/seyonec/project-name
Run page: https://wandb.ai/seyonec/project-name/runs/1t7dyfs4
Run data is saved locally in /content/bert-loves-chemistry/wandb/run-20210318_145336-1t7dyfs4

Running Epoch 0 of 10: 0%| | 0/148 [00:00<?, ?it/s]

/usr/local/lib/python3.7/dist-packages/torch/nn/modules/module.py:760: UserWarning: Using non-full backward hook
s on a Module that does not return a single Tensor or a tuple of Tensors is deprecated and will be removed in fu
ture versions. This hook will be missing some of the grad_output. Please use register_full_backward_hook to get
the documented behavior.
warnings.warn("Using non-full backward hooks on a Module that does not return a "
/usr/local/lib/python3.7/dist-packages/torch/nn/modules/module.py:795: UserWarning: Using a non-full backward ho
ok when the forward contains multiple autograd Nodes is deprecated and will be removed in future versions. This
hook will be missing some grad_input. Please use register_full_backward_hook to get the documented behavior.
warnings.warn("Using a non-full backward hook when the forward contains multiple autograd Nodes "
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INFO:simpletransformers.classification.classification_model: Training of roberta model complete. Saved to /conte
nt/BPE_PubChem_10M_ClinTox_run.
(1480, 0.10153530814545406)

Let's install scikit-learn now, to evaluate the model we've trained. We will be using the accuracy and PRC-AUC metrics
(average precision score).

import sklearn

# accuracy
result, model_outputs, wrong_predictions = model.eval_model(test_df, acc=sklearn.metrics.accuracy_score)

# ROC-PRC
result, model_outputs, wrong_predictions = model.eval_model(test_df, acc=sklearn.metrics.average_precision_score)

INFO:simpletransformers.classification.classification_utils: Converting to features started. Cache is not used.

INFO:simpletransformers.classification.classification_utils: Saving features into cached file cache_dir/cached_d
ev_roberta_128_2_148
Running Evaluation: 0%| | 0/19 [00:00<?, ?it/s]
INFO:simpletransformers.classification.classification_model: Initializing WandB run for evaluation.
Finishing last run (ID:1t7dyfs4) before initializing another...
Waiting for W&B process to finish, PID 4627

Program ended successfully.

VBox(children=(Label(value=' 0.01MB of 0.01MB uploaded (0.00MB deduped)\r'), FloatProgress(value=1.0, max=1.0)…
Find user logs for this run at: /content/bert-loves-chemistry/wandb/run-20210318_145336-
1t7dyfs4/logs/debug.log
Find internal logs for this run at: /content/bert-loves-chemistry/wandb/run-20210318_145336-
1t7dyfs4/logs/debug-internal.log

Run summary:

Training loss 0.0003

lr 0.0

global_step 1450

_runtime 116

_timestamp 1616079332

_step 28

Run history:

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Synced 5 W&B file(s), 1 media file(s), 0 artifact file(s) and 0 other file(s)

Synced snowy-firefly-250: https://wandb.ai/seyonec/project-name/runs/1t7dyfs4

...Successfully finished last run (ID:1t7dyfs4). Initializing new run:

Tracking run with wandb version 0.10.22

Syncing run summer-pyramid-251 to Weights & Biases (Documentation).
Project page: https://wandb.ai/seyonec/project-name
Run page: https://wandb.ai/seyonec/project-name/runs/a6brkv9i
Run data is saved locally in /content/bert-loves-chemistry/wandb/run-20210318_145535-a6brkv9i

INFO:simpletransformers.classification.classification_model:{'mcc': 0.664470436990577, 'tp': 138, 'tn': 5, 'fp':

4, 'fn': 1, 'auroc': 0.8281374900079936, 'auprc': 0.9855371861072479, 'acc': 0.9662162162162162, 'eval_loss': 0.
2469284737426757}
INFO:simpletransformers.classification.classification_utils: Converting to features started. Cache is not used.
INFO:simpletransformers.classification.classification_utils: Saving features into cached file cache_dir/cached_d
ev_roberta_128_2_148
Running Evaluation: 0%| | 0/19 [00:00<?, ?it/s]
INFO:simpletransformers.classification.classification_model: Initializing WandB run for evaluation.
Finishing last run (ID:a6brkv9i) before initializing another...

Waiting for W&B process to finish, PID 4677

Program ended successfully.
VBox(children=(Label(value=' 0.00MB of 0.00MB uploaded (0.00MB deduped)\r'), FloatProgress(value=1.0, max=1.0)…
Find user logs for this run at: /content/bert-loves-chemistry/wandb/run-20210318_145535-
a6brkv9i/logs/debug.log
Find internal logs for this run at: /content/bert-loves-chemistry/wandb/run-20210318_145535-
a6brkv9i/logs/debug-internal.log
Run summary:

_runtime 3

_timestamp 1616079341

_step 2

Run history:

_runtime ▁▁▁

_timestamp ▁▁▁

_step ▁▅█

Synced 5 W&B file(s), 3 media file(s), 0 artifact file(s) and 0 other file(s)

Synced summer-pyramid-251: https://wandb.ai/seyonec/project-name/runs/a6brkv9i

...Successfully finished last run (ID:a6brkv9i). Initializing new run:

Tracking run with wandb version 0.10.22

Syncing run vivid-morning-252 to Weights & Biases (Documentation).
Project page: https://wandb.ai/seyonec/project-name
Run page: https://wandb.ai/seyonec/project-name/runs/7bl6wyef
Run data is saved locally in /content/bert-loves-chemistry/wandb/run-20210318_145541-7bl6wyef

INFO:simpletransformers.classification.classification_model:{'mcc': 0.664470436990577, 'tp': 138, 'tn': 5, 'fp':

4, 'fn': 1, 'auroc': 0.8281374900079936, 'auprc': 0.9855371861072479, 'acc': 0.9715961528455196, 'eval_loss': 0.
2469284737426757}

The model performs pretty well, averaging above 97% ROC-PRC after training on only ~1400 data samples and 150
positive leads in a couple of minutes! We can clearly see the predictive power of transfer learning, and approaches like
these are becoming increasing popular in the pharmaceutical industry where larger datasets are scarce. By training on
more epochs and tasks, we can probably boost the accuracy as well!

Lets evaluate the model on one last string from ClinTox's test set for toxicity. The model should predict 1, meaning the
drug failed clinical trials for toxicity reasons and wasn't approved by the FDA.

# Lets input a molecule with a toxicity value of 1

predictions, raw_outputs = model.predict(['C1=C(C(=O)NC(=O)N1)F'])

INFO:simpletransformers.classification.classification_utils: Converting to features started. Cache is not used.

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print(predictions)
print(raw_outputs)

[1]
[[-4.51171875 4.58203125]]

The model predicts the sample correctly! Some future tasks may include using the same model on multiple tasks (Tox21
provides multiple tasks relating to different biochemical pathways for toxicity, as an example), through multi-task
classification, as well as training on a larger dataset such as HIV, one of the other harder tasks in molecular machine
learning. This will be expanded on in future work!

Benchmarking Smiles-Tokenizer ChemBERTa models on

ClinTox
Now lets compare how this model performs to a similar variant of ChemBERTa, that utilizes a different tokenizer, the
SmilesTokenizer which is built-in to DeepChem! Let see if using a tokenizer which splits SMILES sequences into
syntatically relevant chemical tokens performs differently, especially on molecular property prediction.

First off, lets initialize this variant model:

from simpletransformers.classification import ClassificationModel, ClassificationArgs

model = ClassificationModel('roberta', 'seyonec/SMILES_tokenized_PubChem_shard00_160k', args={'evaluate_each_epoch'

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Some weights of the model checkpoint at seyonec/SMILES_tokenized_PubChem_shard00_160k were not used when initial
izing RobertaForSequenceClassification: ['lm_head.bias', 'lm_head.dense.weight', 'lm_head.dense.bias', 'lm_head.
layer_norm.weight', 'lm_head.layer_norm.bias', 'lm_head.decoder.weight', 'lm_head.decoder.bias']
- This IS expected if you are initializing RobertaForSequenceClassification from the checkpoint of a model train
ed on another task or with another architecture (e.g. initializing a BertForSequenceClassification model from a
BertForPreTraining model).
- This IS NOT expected if you are initializing RobertaForSequenceClassification from the checkpoint of a model t
hat you expect to be exactly identical (initializing a BertForSequenceClassification model from a BertForSequenc
eClassification model).
Some weights of RobertaForSequenceClassification were not initialized from the model checkpoint at seyonec/SMILE
S_tokenized_PubChem_shard00_160k and are newly initialized: ['classifier.dense.weight', 'classifier.dense.bias',
'classifier.out_proj.weight', 'classifier.out_proj.bias']
You should probably TRAIN this model on a down-stream task to be able to use it for predictions and inference.
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Special tokens have been added in the vocabulary, make sure the associated word embedding are fine-tuned or trai
ned.

print(model.tokenizer)

PreTrainedTokenizer(name_or_path='seyonec/SMILES_tokenized_PubChem_shard00_160k', vocab_size=591, model_max_len=

514, is_fast=False, padding_side='right', special_tokens={'bos_token': AddedToken("<s>", rstrip=False, lstrip=Fa
lse, single_word=False, normalized=True), 'eos_token': AddedToken("</s>", rstrip=False, lstrip=False, single_wor
d=False, normalized=True), 'unk_token': '[UNK]', 'sep_token': '[SEP]', 'pad_token': '[PAD]', 'cls_token': '[CLS]
', 'mask_token': '[MASK]'})

Train Dataset: (1182, 2)

Eval Dataset: (148, 2)
TEST Dataset: (148, 2)

!wandb login

wandb: Currently logged in as: seyonec (use `wandb login --relogin` to force relogin)

# Create directory to store model weights (change path accordingly to where you want!)
!mkdir SmilesTokenizer_PubChem_10M_ClinTox_run
# Train the model
model.train_model(train_df, eval_df=valid_df, output_dir='/content/SmilesTokenizer_PubChem_10M_ClinTox_run', args={

INFO:simpletransformers.classification.classification_utils: Converting to features started. Cache is not used.

Waiting for W&B process to finish, PID 4711

Program ended successfully.
VBox(children=(Label(value=' 0.00MB of 0.00MB uploaded (0.00MB deduped)\r'), FloatProgress(value=1.0, max=1.0)…
Find user logs for this run at: /content/bert-loves-chemistry/wandb/run-20210318_145541-
7bl6wyef/logs/debug.log
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s on a Module that does not return a single Tensor or a tuple of Tensors is deprecated and will be removed in fu
ture versions. This hook will be missing some of the grad_output. Please use register_full_backward_hook to get
the documented behavior.
warnings.warn("Using non-full backward hooks on a Module that does not return a "
/usr/local/lib/python3.7/dist-packages/torch/nn/modules/module.py:795: UserWarning: Using a non-full backward ho
ok when the forward contains multiple autograd Nodes is deprecated and will be removed in future versions. This
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nt/SmilesTokenizer_PubChem_10M_ClinTox_run.
(2220, 0.09892498987772685)

Let's install scikit-learn now, to evaluate the model we've trained. We will be using the accuracy and PRC-AUC metrics
(average precision score).

import sklearn

# accuracy
result, model_outputs, wrong_predictions = model.eval_model(test_df, acc=sklearn.metrics.accuracy_score)

# ROC-PRC
result, model_outputs, wrong_predictions = model.eval_model(test_df, acc=sklearn.metrics.average_precision_score)

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Run summary:

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lr 0.0

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INFO:simpletransformers.classification.classification_model:{'mcc': 0.3646523331752495, 'tp': 138, 'tn': 2, 'fp'

: 7, 'fn': 1, 'auroc': 0.8073541167066347, 'auprc': 0.984400271563181, 'acc': 0.9459459459459459, 'eval_loss': 0
.3173560830033047}
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INFO:simpletransformers.classification.classification_model:{'mcc': 0.3646523331752495, 'tp': 138, 'tn': 2, 'fp'

: 7, 'fn': 1, 'auroc': 0.8073541167066347, 'auprc': 0.984400271563181, 'acc': 0.951633958443683, 'eval_loss': 0.
3173560830033047}

The model performs incredibly well, averaging above 96% PRC-AUC after training on only ~1400 data samples and 150
positive leads in a couple of minutes! This model was also trained on 1/10th the amount of pre-training data as the
PubChem-10M BPE model we used previously, but it still showcases robust performance. We can clearly see the
predictive power of transfer learning, and approaches like these are becoming increasing popular in the pharmaceutical
industry where larger datasets are scarce. By training on more epochs and tasks, we can probably boost the accuracy
as well!

# Lets input a molecule with a toxicity value of 1

predictions, raw_outputs = model.predict(['C1=C(C(=O)NC(=O)N1)F'])

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print(predictions)
print(raw_outputs)

[1]
[[-4.546875 4.83984375]]

Congratulations! Time to join the Community!

Star DeepChem on Github

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

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sciences. Join the conversation!
Training a Normalizing Flow on QM9
By Nathan C. Frey | Twitter

In this tutorial, we will train a Normalizing Flow (NF) on the QM9 dataset. The dataset comprises 133,885 stable small
organic molecules made up of CHNOF atoms. We will try to train a network that is an invertible transformation between
a simple base distribution and the distribution of molecules in QM9. One of the key advantages of normalizing flows is
that they can be constructed to efficiently sample from a distribution (generative modeling) and do probability density
calculations (exactly compute log-likelihoods), whereas other models make tradeoffs between the two or can only
approximate probability densities. This work has been published and considered as FastFlows see reference.

NFs are useful whenever we need a probabilistic model with one or both of these capabilities. Note that because NFs are
completely invertible, there is no "latent space" in the sense used when referring to generative adversarial networks or
variational autoencoders. For more on NFs, we refer to this review paper.

To encode the QM9 dataset, we'll make use of the SELFIES (SELF-referencIng Embedded Strings) representation, which
is a 100% robust molecular string representation. SMILES strings produced by generative models are often syntactically
invalid (they do not correspond to a molecular graph), or they violate chemical rules like the maximum number of bonds
between atoms. SELFIES are designed so that even totally random SELFIES strings correspond to valid molecular graphs,
so they are a great framework for generative modeling. For more details about SELFIES, see the GitHub repo and the
associated paper.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!pip install --pre deepchem

import deepchem
deepchem.__version__

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018.9)
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epchem) (2.8.2)
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pandas->deepchem) (1.15.0)
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.2)
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->deepchem) (3.1.0)
'2.6.1'

Install the SELFIES library to translate SMILES strings.

!pip install selfies

Requirement already satisfied: selfies in /usr/local/lib/python3.7/dist-packages (2.0.0)

import numpy as np
import matplotlib.pyplot as plt
import seaborn as sns
import pandas as pd
import os

import deepchem as dc
from deepchem.models.normalizing_flows import NormalizingFlow, NormalizingFlowModel
from deepchem.models.optimizers import Adam
from deepchem.data import NumpyDataset
from deepchem.splits import RandomSplitter
from deepchem.molnet import load_tox21

import rdkit
from rdkit import Chem
from rdkit.Chem.Draw import IPythonConsole
from rdkit.Chem import Draw

from IPython.display import Image, display

import selfies as sf

import tensorflow as tf
import tensorflow_probability as tfp

tfd = tfp.distributions
tfb = tfp.bijectors
tfk = tf.keras

tfk.backend.set_floatx('float64')

First, let's get a dataset of 2500 small organic molecules from the QM9 dataset. We'll then convert the molecules to
SELFIES, one-hot encode them, and dequantize the inputs so they can be processed by a normalizing flow. 2000
molecules will be used for training, while the remaining 500 will be split into validation and test sets. We'll use the
validation set to see how our architecture is doing at learning the underlying the distribution, and leave the test set
alone. You should feel free to experiment with this notebook to get the best model you can and evaluate it on the test
set when you're done!

# Download from MolNet

tasks, datasets, transformers = dc.molnet.load_qm9(featurizer='ECFP')
df = pd.DataFrame(data={'smiles': datasets[0].ids})

data = df[['smiles']].sample(2500, random_state=42)

SELFIES defines a dictionary called bond_constraints that enforces how many bonds every atom or ion can make.
E.g., 'C': 4, 'H': 1, etc. The ? symbol is used for any atom or ion that isn't defined in the dictionary, and it defaults to 8
bonds. Because QM9 contains ions and we don't want to allow those ions to form up to 8 bonds, we'll constrain them to
3. This will really improve the percentage of valid molecules we generate. You can read more about setting constraints
in the SELFIES documentation.

sf.set_semantic_constraints() # reset constraints

constraints = sf.get_semantic_constraints()
constraints['?'] = 3

sf.set_semantic_constraints(constraints)
constraints

{'?': 3,
'B': 3,
'B+1': 2,
'B-1': 4,
'Br': 1,
'C': 4,
'C+1': 5,
'C-1': 3,
'Cl': 1,
'F': 1,
'H': 1,
'I': 1,
'N': 3,
'N+1': 4,
'N-1': 2,
'O': 2,
'O+1': 3,
'O-1': 1,
'P': 5,
'P+1': 6,
'P-1': 4,
'S': 6,
'S+1': 7,
'S-1': 5}

def preprocess_smiles(smiles):
return sf.encoder(smiles)

def keys_int(symbol_to_int):
d={}
i=0
for key in symbol_to_int.keys():
d[i]=key
i+=1
return d

data['selfies'] = data['smiles'].apply(preprocess_smiles)

Let's take a look at some short SMILES strings and their corresponding SELFIES representations. We can see right away
that there is a key difference in how the two representations deal with Rings and Branches. SELFIES is designed so that
branch length and ring size are stored locally with the Branch and Ring identifiers, and the SELFIES grammar
prevents invalid strings.

data['len'] = data['smiles'].apply(lambda x: len(x))

data.sort_values(by='len').head()

smiles selfies len

6728 [H]c1nnc([H])o1 [H][C][=N][N][=C][Branch1][C][H][O][Ring1][=Br... 15

72803 [H]c1nnnc([H])n1 [H][C][=N][N][=N][C][Branch1][C][H][=N][Ring1]... 16

97670 [H]c1onnc1C(F)(F)F [H][C][O][N][=N][C][=Ring1][Branch1][C][Branch... 18

25487 [H]n1nnc(C#CC#N)n1 [H][N][N][=N][C][Branch1][Branch1][C][#C][C][#... 18

32004 [H]C#Cc1nnc(F)nc1[H] [H][C][#C][C][=N][N][=C][Branch1][C][F][N][=C]... 20

To convert SELFIES to a one-hot encoded representation, we need to construct an alphabet of all the characters that
occur in the list of SELFIES strings. We also have to know what the longest SELFIES string is, so that all the shorter
SELFIES can be padded with '[nop]' to be equal length.

selfies_list = np.asanyarray(data.selfies)
selfies_alphabet = sf.get_alphabet_from_selfies(selfies_list)
selfies_alphabet.add('[nop]') # Add the "no operation" symbol as a padding character
selfies_alphabet.add('.')
selfies_alphabet = list(sorted(selfies_alphabet))
largest_selfie_len = max(sf.len_selfies(s) for s in selfies_list)
symbol_to_int = dict((c, i) for i, c in enumerate(selfies_alphabet))
int_mol=keys_int(symbol_to_int)

selfies has a handy utility function to translate SELFIES strings into one-hot encoded vectors.

onehots=sf.batch_selfies_to_flat_hot(selfies_list, symbol_to_int,largest_selfie_len)

Next, we "dequantize" the inputs by adding random noise from the interval [0, 1) to every input in the encodings.
This allows the normalizing flow to operate on continuous inputs (rather than discrete), and the original inputs can easily
be recovered by applying a floor function.

input_tensor = tf.convert_to_tensor(onehots, dtype='float64')

noise_tensor = tf.random.uniform(shape=input_tensor.shape, minval=0, maxval=1, dtype='float64')
dequantized_data = tf.add(input_tensor, noise_tensor)

The dequantized data is ready to be processed as a DeepChem dataset and split into training, validation, and test sets.
We'll also keep track of the SMILES strings for the training set so we can compare the training data to our generated
molecules later on.

ds = NumpyDataset(dequantized_data) # Create a DeepChem dataset

splitter = RandomSplitter()
train, val, test = splitter.train_valid_test_split(dataset=ds, seed=42)
train_idx, val_idx, test_idx = splitter.split(dataset=ds, seed=42)

dim = len(train.X[0]) # length of one-hot encoded vectors

train.X.shape # 2000 samples, N-dimensional one-hot vectors that represent molecules

(2000, 2596)

# SMILES strings of training data

train_smiles = data['smiles'].iloc[train_idx].values

Next we'll set up the normalizing flow model. The base distribution is a multivariate Normal distribution. The
permutation layer permutes the dimensions of the input so that the normalizing flow layers will operate along multiple
dimensions of the inputs. To understand why the permutation is needed, we need to know a bit about how the
normalizing flow architecture works.

base_dist = tfd.MultivariateNormalDiag(loc=np.zeros(dim), scale_diag=np.ones(dim))

if dim % 2 == 0:
permutation = tf.cast(np.concatenate((np.arange(dim / 2, dim), np.arange(0, dim / 2))),
tf.int32)
else:
permutation = tf.cast(np.concatenate((np.arange(dim / 2 + 1, dim), np.arange(0, dim / 2))), tf.int32)

For this simple example, we'll set up a flow of repeating Masked Autoregressive Flow layers. The autoregressive
property is enforced by using the Masked Autoencoder for Distribution Estimation architecture. The layers of the flow
are a bijector, an invertible mapping between the base and target distributions.

MAF takes the inputs from the base distribution and transforms them with a simple scale-and-shift (affine) operation, but
crucially the scale-and-shift for each dimension of the output depends on the previously generated dimensions of the
output. That independence of future dimensions preserves the autoregressive property and ensures that the
normalizing flow is invertible. Now we can see that we need permutations to change the ordering of the inputs, or else
the normalizing flow would only transform certain dimensions of the inputs.

Batch Normalization layers can be added for additional stability in training, but may have strange effects on the outputs
and require some input reshaping to work properly. Increasing num_layers and hidden_units can make more
expressive flows capable of modeling more complex target distributions.

num_layers = 8
flow_layers = []

Made = tfb.AutoregressiveNetwork(params=2,
hidden_units=[512, 512], activation='relu')

for i in range(num_layers):
flow_layers.append(
(tfb.MaskedAutoregressiveFlow(shift_and_log_scale_fn=Made)
))

permutation = tf.cast(np.random.permutation(np.arange(0, dim)), tf.int32)

flow_layers.append(tfb.Permute(permutation=permutation))

# if (i + 1) % int(2) == 0:
# flow_layers.append(tfb.BatchNormalization())

We can draw samples from the untrained distribution, but for now they don't have any relation to the QM9 dataset
distribution.

%%time
nf = NormalizingFlow(base_distribution=base_dist,
flow_layers=flow_layers)

CPU times: user 280 ms, sys: 10.2 ms, total: 290 ms
Wall time: 289 ms

A NormalizingFlowModel takes a NormalizingFlow and any parameters used by deepchem.models.KerasModel .

nfm = NormalizingFlowModel(nf, learning_rate=1e-4, batch_size=128)

Now to train the model! We'll try to minimize the negative log likelihood loss, which measures the likelihood that
generated samples are drawn from the target distribution, i.e. as we train the model, it should get better at modeling
the target distribution and it will generate samples that look like molecules from the QM9 dataset.

losses = []
val_losses = []

%%time
max_epochs = 10 # maximum number of epochs of the training

for epoch in range(max_epochs):

loss = nfm.fit(train, nb_epoch=1, all_losses=losses)
val_loss = nfm.create_nll(val.X)
val_losses.append(val_loss.numpy())

WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
WARNING:tensorflow:Model was constructed with shape (None, 2596) for input KerasTensor(type_spec=TensorSpec(shap
e=(None, 2596), dtype=tf.float64, name='input_1'), name='input_1', description="created by layer 'input_1'"), bu
t it was called on an input with incompatible shape (1, 128, 2596).
CPU times: user 13min 40s, sys: 20.9 s, total: 14min 1s
Wall time: 7min 27s

f, ax = plt.subplots()
ax.scatter(range(len(losses)), losses, label='train loss')
ax.scatter(range(len(val_losses)), val_losses, label='val loss')
plt.legend(loc='upper right');

The normalizing flow is learning a mapping between the multivariate Gaussian and the target distribution! We can see
this by visualizing the loss on the validation set. We can now use nfm.flow.sample() to generate new QM9-like
molecules and nfm.flow.log_prob() to evaluate the likelihood that a molecule was drawn from the underlying
distribution.

generated_samples = nfm.flow.sample(10) # generative modeling

log_probs = nfm.flow.log_prob(generated_samples) # probability density estimation

Now we transform the generated samples back into SELFIES. We have to quantize the outputs and add padding
characters to any one-hot encoding vector that has all zeros.

mols = tf.math.floor(generated_samples) # quantize data

mols = tf.clip_by_value(mols, 0, 1) # Set negative values to 0 and values > 1 to 1
mols_list = mols.numpy().tolist()

# Add padding characters if needed

for mol in mols_list:
for i in range(largest_selfie_len):
row = mol[len(selfies_alphabet) * i: len(selfies_alphabet) * (i + 1)]
if all(elem == 0 for elem in row):
mol[len(selfies_alphabet) * (i+1) - 1] = 1

selfies has another utility function to translate one-hot encoded representations back to SELFIES strings.

mols=sf.batch_flat_hot_to_selfies(mols_list, int_mol)

We can use RDKit to find valid generated molecules. Some have unphysical valencies and should be discarded. If you've
ever tried to generate valid SMILES strings, you'll notice right away that this model is doing much better than we would
expect! Using SELFIES, 90% of the generated molecules are valid, even though our normalizing flow architecture doesn't
know any rules that govern chemical validity.

from rdkit import RDLogger

from rdkit import Chem
RDLogger.DisableLog('rdApp.*') # suppress error messages

valid_count = 0
valid_selfies, invalid_selfies = [], []
for idx, selfies in enumerate(mols):
try:
if Chem.MolFromSmiles(sf.decoder(mols[idx]), sanitize=True) is not None:
valid_count += 1
valid_selfies.append(selfies)
else:
invalid_selfies.append(selfies)
except Exception:
pass
print('%.2f' % (valid_count / len(mols)), '% of generated samples are valid molecules.')

1.00 % of generated samples are valid molecules.

Let's take a look at some of the generated molecules! We'll borrow some helper functions from the Modeling Solubility
tutorial to display molecules with RDKit.
gen_mols = [Chem.MolFromSmiles(sf.decoder(vs)) for vs in valid_selfies]

def display_images(filenames):
"""Helper to pretty-print images."""
for file in filenames:
display(Image(file))

def mols_to_pngs(mols, basename="generated_mol"):

"""Helper to write RDKit mols to png files."""
filenames = []
for i, mol in enumerate(mols):
filename = "%s%d.png" % (basename, i)
Draw.MolToFile(mol, filename)
filenames.append(filename)
return filenames

display_mols = []
for i in range(10):
display_mols.append(gen_mols[i])

display_images(mols_to_pngs(display_mols))
Finally, we can compare generated molecules with our training data via a similarity search with Tanimoto similarity. This
gives an indication of how "original" the generated samples are, versus simply producing samples that are extremely
similar to molecules the model has already seen. We have to keep in mind that QM9 contains all stable small molecules
with up to 9 heavy atoms (CONF). So anything new we generate either exists in the full QM9 dataset, or else will not
obey the charge neutrality and stability criteria used to generated QM9.

from rdkit.Chem.Fingerprints.FingerprintMols import FingerprintMol

from rdkit.DataStructs import FingerprintSimilarity
from IPython.display import display

def tanimoto_similarity(database_mols, query_mol):

"""Compare generated molecules to database by Tanimoto similarity."""
# convert Mol to datastructure type
fps = [FingerprintMol(m) for m in database_mols]

# set a query molecule to compare against database

query = FingerprintMol(query_mol)

similarities = []

# loop through to find Tanimoto similarity

for idx, f in enumerate(fps):
# tuple: (idx, similarity)
similarities.append((idx, FingerprintSimilarity(query, f)))

# sort sim using the similarities

similarities.sort(key=lambda x:x[1], reverse=True)

return similarities

We'll consider our generated molecules and look at the top 3 most similar molecules from the training data by Tanimoto
similarity. Here's an example where the Tanimoto similarity scores are medium. There are molecules in our training set
that are similar to our generated sample. This might be interesting, or it might mean that the generated molecule is
unrealistic.

train_mols = [Chem.MolFromSmiles(smiles) for smiles in train_smiles]

# change the second argument to compare different generated molecules to QM9

tanimoto_scores = tanimoto_similarity(train_mols, gen_mols[3])
similar_mols = []

for idx, ts in tanimoto_scores[:3]:

print(round(ts, 3))
similar_mols.append(train_mols[idx])

display_images(mols_to_pngs(similar_mols, 'qm9_mol'))

0.521
0.471
0.468
Molecules of the previous tutorial:
These molecules were obteined through sampling.

Comparing with the tanimoto similarity:

With scores of:

0.243
0.243
0.241

Further reading
So far we have looked at a measure of validity and done a bit of investigation into the novelty of the generated
compounds. There are more dimensions along which we can and should evaluate the performance of a generative
model. For an example of some standard benchmarks, see the GuacaMol evaluation framework.

For more information about FastFlows look at this paper where the workflow is crearly explained.

For examples of normalizing flow-based molecular graph generation frameworks, check out the MoFlow, GraphAF, and
GraphNVP papers.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Screening Zinc For HIV Inhibition
In this tutorial we will walk through how to efficiently screen a large compound library with DeepChem (ZINC). Screening
a large compound library using machine learning is a CPU bound pleasingly parrellel problem. The actual code examples
I will use assume the resources available are a single very big machine (like an AWS c5.18xlarge), but should be readily
swappable for other systmes (like a super computing cluster). At a high level what we will do is...

1. Create a Machine Learning Model Over Labeled Data

2. Transform ZINC into "Work-Units"
3. Create an inference script which runs predictions over a "Work-Unit"
4. Load "Work-Unit" into a "Work Queue"
5. Consume work units from "Work Queue"
6. Gather Results

This tutorial is unlike the previous tutorials in that it's designed to be run on AWS rather than on Google Colab. That's
because we'll need access to a large machine with many cores to do this computation efficiently. We'll try to provide
details about how to do this throughout the tutorial.

1. Train Model On Labelled Data

We are just going to knock out a simple model here. In a real world problem you will probably try several models and do
a little hyper parameter searching.

from deepchem.molnet.load_function import hiv_datasets

/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/sklearn/externals/joblib/__init__.py:15:
FutureWarning: sklearn.externals.joblib is deprecated in 0.21 and will be removed in 0.23. Please import this fu
nctionality directly from joblib, which can be installed with: pip install joblib. If this warning is raised whe
n loading pickled models, you may need to re-serialize those models with scikit-learn 0.21+.
warnings.warn(msg, category=FutureWarning)
RDKit WARNING: [18:15:24] Enabling RDKit 2019.09.3 jupyter extensions
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/framework/dtypes.py:516
: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy,
it will be understood as (type, (1,)) / '(1,)type'.
_np_qint8 = np.dtype([("qint8", np.int8, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/framework/dtypes.py:517
: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy,
it will be understood as (type, (1,)) / '(1,)type'.
_np_quint8 = np.dtype([("quint8", np.uint8, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/framework/dtypes.py:518
: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy,
it will be understood as (type, (1,)) / '(1,)type'.
_np_qint16 = np.dtype([("qint16", np.int16, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/framework/dtypes.py:519
: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy,
it will be understood as (type, (1,)) / '(1,)type'.
_np_quint16 = np.dtype([("quint16", np.uint16, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/framework/dtypes.py:520
: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy,
it will be understood as (type, (1,)) / '(1,)type'.
_np_qint32 = np.dtype([("qint32", np.int32, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/framework/dtypes.py:525
: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of numpy,
it will be understood as (type, (1,)) / '(1,)type'.
np_resource = np.dtype([("resource", np.ubyte, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorboard/compat/tensorflow_stub/dtypes
.py:541: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of
numpy, it will be understood as (type, (1,)) / '(1,)type'.
_np_qint8 = np.dtype([("qint8", np.int8, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorboard/compat/tensorflow_stub/dtypes
.py:542: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of
numpy, it will be understood as (type, (1,)) / '(1,)type'.
_np_quint8 = np.dtype([("quint8", np.uint8, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorboard/compat/tensorflow_stub/dtypes
.py:543: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of
numpy, it will be understood as (type, (1,)) / '(1,)type'.
_np_qint16 = np.dtype([("qint16", np.int16, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorboard/compat/tensorflow_stub/dtypes
.py:544: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of
numpy, it will be understood as (type, (1,)) / '(1,)type'.
_np_quint16 = np.dtype([("quint16", np.uint16, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorboard/compat/tensorflow_stub/dtypes
.py:545: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of
numpy, it will be understood as (type, (1,)) / '(1,)type'.
_np_qint32 = np.dtype([("qint32", np.int32, 1)])
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorboard/compat/tensorflow_stub/dtypes
.py:550: FutureWarning: Passing (type, 1) or '1type' as a synonym of type is deprecated; in a future version of
numpy, it will be understood as (type, (1,)) / '(1,)type'.
np_resource = np.dtype([("resource", np.ubyte, 1)])

from deepchem.models import GraphConvModel

from deepchem.data import NumpyDataset
from sklearn.metrics import average_precision_score
import numpy as np

tasks, all_datasets, transformers = hiv_datasets.load_hiv(featurizer="GraphConv")

train, valid, test = [NumpyDataset.from_DiskDataset(x) for x in all_datasets]
model = GraphConvModel(1, mode="classification")
model.fit(train)
Loading raw samples now.
shard_size: 8192
About to start loading CSV from /var/folders/st/ds45jcqj2232lvhr0y9qt5sc0000gn/T/HIV.csv
Loading shard 1 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 0 took 12.479 s
Loading shard 2 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 1 took 13.668 s
Loading shard 3 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 2 took 13.550 s
Loading shard 4 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
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Featurizing sample 8000
TIMING: featurizing shard 3 took 13.173 s
Loading shard 5 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
RDKit WARNING: [18:16:53] WARNING: not removing hydrogen atom without neighbors
RDKit WARNING: [18:16:53] WARNING: not removing hydrogen atom without neighbors
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 4 took 13.362 s
Loading shard 6 of size 8192.
Featurizing sample 0
TIMING: featurizing shard 5 took 0.355 s
TIMING: dataset construction took 80.394 s
Loading dataset from disk.
TIMING: dataset construction took 16.676 s
Loading dataset from disk.
TIMING: dataset construction took 7.529 s
Loading dataset from disk.
TIMING: dataset construction took 7.796 s
Loading dataset from disk.
TIMING: dataset construction took 17.521 s
Loading dataset from disk.
TIMING: dataset construction took 7.770 s
Loading dataset from disk.
TIMING: dataset construction took 7.873 s
Loading dataset from disk.
TIMING: dataset construction took 15.495 s
Loading dataset from disk.
TIMING: dataset construction took 1.959 s
Loading dataset from disk.
TIMING: dataset construction took 1.949 s
Loading dataset from disk.
WARNING:tensorflow:From /Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python
/ops/init_ops.py:1251: calling VarianceScaling.__init__ (from tensorflow.python.ops.init_ops) with dtype is depr
ecated and will be removed in a future version.
Instructions for updating:
Call initializer instance with the dtype argument instead of passing it to the constructor
WARNING:tensorflow:Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c0
48>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c048>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c048>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c048>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e
80>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e80>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e80>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e80>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa
90>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa90>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa90>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa90>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d1
98>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d198>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d198>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d198>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43
f3a940>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When fi
ling the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Ca
use: converting <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43f3a940>>:
AttributeError: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43f3a940>> c
ould not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the b
ug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: conve
rting <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43f3a940>>: AttributeE
rror: module 'gast' has no attribute 'Num'
WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/layers.py:222: The name tf.unsorted_segment
_sum is deprecated. Please use tf.math.unsorted_segment_sum instead.

WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/layers.py:224: The name tf.unsorted_segment

_max is deprecated. Please use tf.math.unsorted_segment_max instead.

WARNING:tensorflow:Entity <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput ob

ject at 0x1a41a9ecf8>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph
team. When filing the bug, set the verbosity to 10 (on Linux, `export AUTOGRAPH_VERBOSITY=10`) and attach the fu
ll output. Cause: converting <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput
object at 0x1a41a9ecf8>>: AttributeError: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput object at 0x
1a41a9ecf8>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. Whe
n filing the bug, set the verbosity to 10 (on Linux, `export AUTOGRAPH_VERBOSITY=10`) and attach the full output
. Cause: converting <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput object a
t 0x1a41a9ecf8>>: AttributeError: module 'gast' has no attribute 'Num'
WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/keras_model.py:169: The name tf.Session is
deprecated. Please use tf.compat.v1.Session instead.

WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/optimizers.py:76: The name tf.train.AdamOpt

imizer is deprecated. Please use tf.compat.v1.train.AdamOptimizer instead.

WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/keras_model.py:258: The name tf.global_vari

ables is deprecated. Please use tf.compat.v1.global_variables instead.
WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/keras_model.py:260: The name tf.variables_i
nitializer is deprecated. Please use tf.compat.v1.variables_initializer instead.

WARNING:tensorflow:Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c0

48>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c048>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c048>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a3e35c048>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e
80>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e80>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e80>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a41856e80>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa
90>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa90>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa90>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphConv.call of <deepchem.models.layers.GraphConv object at 0x1a49f5aa90>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d1
98>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing
the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause:
converting <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d198>>: Attribute
Error: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d198>> could
not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the bug, s
et the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: converting
<bound method GraphPool.call of <deepchem.models.layers.GraphPool object at 0x1a43f5d198>>: AttributeError: modu
le 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43
f3a940>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When fi
ling the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Ca
use: converting <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43f3a940>>:
AttributeError: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43f3a940>> c
ould not be transformed and will be executed as-is. Please report this to the AutgoGraph team. When filing the b
ug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output. Cause: conve
rting <bound method GraphGather.call of <deepchem.models.layers.GraphGather object at 0x1a43f3a940>>: AttributeE
rror: module 'gast' has no attribute 'Num'
WARNING:tensorflow:Entity <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput ob
ject at 0x1a41a9ecf8>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph
team. When filing the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the fu
ll output. Cause: converting <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput
object at 0x1a41a9ecf8>>: AttributeError: module 'gast' has no attribute 'Num'
WARNING: Entity <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput object at 0x
1a41a9ecf8>> could not be transformed and will be executed as-is. Please report this to the AutgoGraph team. Whe
n filing the bug, set the verbosity to 10 (on Linux, èxport AUTOGRAPH_VERBOSITY=10`) and attach the full output
. Cause: converting <bound method TrimGraphOutput.call of <deepchem.models.graph_models.TrimGraphOutput object a
t 0x1a41a9ecf8>>: AttributeError: module 'gast' has no attribute 'Num'
WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/losses.py:108: The name tf.losses.softmax_c
ross_entropy is deprecated. Please use tf.compat.v1.losses.softmax_cross_entropy instead.

WARNING:tensorflow:From /Users/bharath/Code/deepchem/deepchem/models/losses.py:109: The name tf.losses.Reduction

is deprecated. Please use tf.compat.v1.losses.Reduction instead.

WARNING:tensorflow:From /Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python
/ops/math_grad.py:318: add_dispatch_support.<locals>.wrapper (from tensorflow.python.ops.array_ops) is deprecate
d and will be removed in a future version.
Instructions for updating:
Use tf.where in 2.0, which has the same broadcast rule as np.where
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/ops/gradients_util.py:9
3: UserWarning: Converting sparse IndexedSlices to a dense Tensor of unknown shape. This may consume a large amo
unt of memory.
"Converting sparse IndexedSlices to a dense Tensor of unknown shape. "
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/ops/gradients_util.py:9
3: UserWarning: Converting sparse IndexedSlices to a dense Tensor of unknown shape. This may consume a large amo
unt of memory.
"Converting sparse IndexedSlices to a dense Tensor of unknown shape. "
/Users/bharath/opt/anaconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/ops/gradients_util.py:9
3: UserWarning: Converting sparse IndexedSlices to a dense Tensor of unknown shape. This may consume a large amo
unt of memory.
"Converting sparse IndexedSlices to a dense Tensor of unknown shape. "
0.0

y_true = np.squeeze(valid.y)
y_pred = model.predict(valid)[:,0,1]
print("Average Precision Score:%s" % average_precision_score(y_true, y_pred))
sorted_results = sorted(zip(y_pred, y_true), reverse=True)
hit_rate_100 = sum(x[1] for x in sorted_results[:100]) / 100
print("Hit Rate Top 100: %s" % hit_rate_100)

Average Precision Score:0.19783388433313015

Hit Rate Top 100: 0.37

Retrain Model Over Full Dataset For The Screen

tasks, all_datasets, transformers = hiv_datasets.load_hiv(featurizer="GraphConv", split=None)

model = GraphConvModel(1, mode="classification", model_dir="/tmp/zinc/screen_model")

model.fit(all_datasets[0])
Loading raw samples now.
shard_size: 8192
About to start loading CSV from /tmp/HIV.csv
Loading shard 1 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 0 took 15.701 s
Loading shard 2 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 1 took 15.869 s
Loading shard 3 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 2 took 19.106 s
Loading shard 4 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 3 took 16.267 s
Loading shard 5 of size 8192.
Featurizing sample 0
Featurizing sample 1000
Featurizing sample 2000
Featurizing sample 3000
Featurizing sample 4000
Featurizing sample 5000
Featurizing sample 6000
Featurizing sample 7000
Featurizing sample 8000
TIMING: featurizing shard 4 took 16.754 s
Loading shard 6 of size 8192.
Featurizing sample 0
TIMING: featurizing shard 5 took 0.446 s
TIMING: dataset construction took 98.214 s
Loading dataset from disk.
TIMING: dataset construction took 21.127 s
Loading dataset from disk.
/home/leswing/miniconda3/envs/deepchem/lib/python3.6/site-packages/tensorflow/python/ops/gradients_impl.py:100:
UserWarning: Converting sparse IndexedSlices to a dense Tensor of unknown shape. This may consume a large amount
of memory.
"Converting sparse IndexedSlices to a dense Tensor of unknown shape. "

2. Create Work-Units
1. Download All of ZINC15.

Go to http://zinc15.docking.org/tranches/home and download all non-empty tranches in .smi format. I found it easiest to
download the wget script and then run the wget script. For the rest of this tutorial I will assume zinc was downloaded to
/tmp/zinc.

The way zinc downloads the data isn't great for inference. We want "Work-Units" which a single CPU can execute that
takes a resonable amount of time (10 minutes to an hour). To accomplish this we are going to split the zinc data into
files each with 500 thousand lines.

mkdir /tmp/zinc/screen
find /tmp/zinc -name '*.smi' -exec cat {} \; | grep -iv "smiles" \
| split -l 500000 /tmp/zinc/screen/segment
This bash command

1. Finds all smi files

2. prints to stdout the contents of the file
3. removes header lines
4. splits into multiple files in /tmp/zinc/screen that are 500k molecules long

3. Creat Inference Script

Now that we have work unit we need to construct a program which ingests a work unit and logs the result. It is
important that the logging mechanism is thread safe! For this example we will get the work unit via a file-path, and log
the result to a file. An easy extensions to distribute over multiple computers would be to get the work unit via a url, and
log the results to a distributed queue.

Here is what mine looks like

inference.py

import sys
import deepchem as dc
import numpy as np
from rdkit import Chem
import pickle
import os

def create_dataset(fname, batch_size=50000):

featurizer = dc.feat.ConvMolFeaturizer()
fin = open(fname)
mols, orig_lines = [], []
for line in fin:
line = line.strip().split()
try:
mol = Chem.MolFromSmiles(line[0])
if mol is None:
continue
mols.append(mol)
orig_lines.append(line)
except:
pass
if len(mols) > 0 and len(mols) % batch_size == 0:
features = featurizer.featurize(mols)
y = np.ones(shape=(len(mols), 1))
ds = dc.data.NumpyDataset(features, y)
yield ds, orig_lines
mols, orig_lines = [], []
if len(mols) > 0:
features = featurizer.featurize(mols)
y = np.ones(shape=(len(mols), 1))
ds = dc.data.NumpyDataset(features, y)
yield ds, orig_lines

def evaluate(fname):
fout_name = "%s_out.smi" % fname
model = dc.models.TensorGraph.load_from_dir('screen_model')
for ds, lines in create_dataset(fname):
y_pred = np.squeeze(model.predict(ds), axis=1)
with open(fout_name, 'a') as fout:
for index, line in enumerate(lines):
line.append(y_pred[index][1])
line = [str(x) for x in line]
line = "\t".join(line)
fout.write("%s\n" % line)

if __name__ == "__main__":
evaluate(sys.argv[1])
4. Load "Work-Unit" into a "Work Queue"
We are going to use a flat file as our distribution mechanism. It will be a bash script calling our inference script for every
work unit. If you are at an academic institution this would be queing your jobs in pbs/qsub/slurm. An option for cloud
computing would be rabbitmq or kafka.

import os
work_units = os.listdir('/tmp/zinc/screen')
with open('/tmp/zinc/work_queue.sh', 'w') as fout:
fout.write("#!/bin/bash\n")
for work_unit in work_units:
full_path = os.path.join('/tmp/zinc', work_unit)
fout.write("python inference.py %s" % full_path)

5. Consume work units from "distribution mechanism"

We will consume work units from our work queue using a very simple Process Pool. It takes lines from our "Work Queue"
and runs them, running as many processes in parrallel as we have cpus. If you are using a supercomputing cluster
system like pbs/qsub/slurm it will take care of this for you. The key is to use one CPU per work unit to get highest
throughput. We accomplish that here using the linux utility "taskset".

Using an c5.18xlarge on aws this will finish overnight.

process_pool.py

import multiprocessing
import sys
from multiprocessing.pool import Pool

import delegator

def run_command(args):
q, command = args
cpu_id = q.get()
try:
command = "taskset -c %s %s" % (cpu_id, command)
print("running %s" % command)
c = delegator.run(command)
print(c.err)
print(c.out)
except Exception as e:
print(e)
q.put(cpu_id)

def main(n_processors, command_file):

commands = [x.strip() for x in open(command_file).readlines()]
commands = list(filter(lambda x: not x.startswith("#"), commands))
q = multiprocessing.Manager().Queue()
for i in range(n_processors):
q.put(i)
argslist = [(q, x) for x in commands]
pool = Pool(processes=n_processors)
pool.map(run_command, argslist)

if __name__ == "__main__":
processors = multiprocessing.cpu_count()
main(processors, sys.argv[1])
>> python process_pool.py /tmp/zinc/work_queue.sh

6. Gather Results
Since we logged our results to *_out.smi we now need to gather all of them up and sort them by our predictions. The
resulting file wile be > 40GB. To analyze the data further you can use dask, or put the data in a rdkit postgres cartridge.

Here I show how to join the and sort the data to get the "best" results.

find /tmp/zinc -name '*_out.smi' -exec cat {} \; > /tmp/zinc/screen/results.smi

sort -rg -k 3,3 /tmp/zinc/screen/results.smi > /tmp/zinc/screen/sorted_results.smi
# Put the top 100k scoring molecules in their own file
head -n 50000 /tmp/zinc/screen/sorted_results.smi > /tmp/zinc/screen/top_100k.smi
/tmp/zinc/screen/top_100k.smi is now a small enough file to investigate using standard tools like pandas.

from rdkit import Chem

from rdkit.Chem.Draw import IPythonConsole
from IPython.display import SVG
from rdkit.Chem.Draw import rdMolDraw2D
best_mols = [Chem.MolFromSmiles(x.strip().split()[0]) for x in open('/tmp/zinc/screen/top_100k.smi').readlines()[:100
best_scores = [x.strip().split()[2] for x in open('/tmp/zinc/screen/top_100k.smi').readlines()[:100]]

print(best_scores[0])
best_mols[0]

0.98874843

print(best_scores[0])
best_mols[1]

0.98874843

print(best_scores[0])
best_mols[2]

0.98874843

print(best_scores[0])
best_mols[3]

0.98874843

The screen seems to favor molecules with one or multiple sulfur trioxides. The top scoring molecules also have low
diversity. When creating a "buy list" we want to optimize for more things than just activity, for instance diversity and
drug like MPO.

#We use the code from https://github.com/PatWalters/rd_filters, detailed explanation is here: http://practicalcheminf
#We will run the PAINS filter on best_mols as suggested by Issue 1355 (https://github.com/deepchem/deepchem/issues/13
import os

import pandas as pd
from rdkit import Chem
from rdkit.Chem.Descriptors import MolWt, MolLogP, NumHDonors, NumHAcceptors, TPSA
from rdkit.Chem.rdMolDescriptors import CalcNumRotatableBonds

#First we get the rules from alert_collection.csv and then filter to get PAINS filter
rule_df = pd.read_csv(os.path.join(os.path.abspath(''), 'assets', 'alert_collection.csv'))
rule_df = rule_df[rule_df['rule_set_name']=='PAINS']
rule_list = []
for rule_id, smarts, max_val, desc in rule_df[["rule_id", "smarts", "max", "description"]].values.tolist():
smarts_mol = Chem.MolFromSmarts(smarts)
if smarts_mol:
rule_list.append((smarts_mol, max_val, desc))

def evaluate(smile):
mol = Chem.MolFromSmiles(smile)
if mol is None:
return [smile, "INVALID", -999, -999, -999, -999, -999, -999]
desc_list = [MolWt(mol), MolLogP(mol), NumHDonors(mol), NumHAcceptors(mol), TPSA(mol), CalcNumRotatableBonds(mol
for patt, max_val, desc in rule_list:
if len(mol.GetSubstructMatches(patt)) > max_val:
return [smiles, desc + " > %d" % (max_val)] +desc_list
return [smiles, "OK"]+desc_list

smiles = [x.strip().split()[0] for x in open('/tmp/zinc/screen/top_100k.smi').readlines()[:100]] # obtain the smiles

res = list(map(evaluate, smiles)) # here we apply the PAINS filter

df = pd.DataFrame(res, columns=["SMILES", "FILTER", "MW", "LogP", "HBD", "HBA", "TPSA", "Rot"])

df_ok = df[
(df.FILTER == "OK") &
df.MW.between(*[0, 500]) & # MW
df.LogP.between(*[-5, 5]) & #LogP
df.HBD.between(*[0, 5]) & #HBD
df.HBA.between(*[0, 10]) & #HBA
df.TPSA.between(*[0, 200]) & #TPSA
df.Rot.between(*[0, 10]) #Rot
]

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Introduction to the Molecular Attention Transformer.
In this tutorial we will learn more about the Molecular Attention Transformer, or MAT. MAT is a model based on
transformers, aimed towards performing molecular prediction tasks. MAT is easy to tune and performs quite well
relative to other molecular prediction tasks. The weights from MAT are chemically interpretable, thus making the model
quite useful.

Reference Paper: Molecular Attention Transformer, Maziarka et. al.

In this tutorial, we will explore how to train MAT, and predict hydration enthalpy values for molecules from the freesolv
hydration enthalpy dataset with MAT.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

Import required modules

import deepchem as dc
from deepchem.models.torch_models import MATModel
from deepchem.feat import MATFeaturizer
import matplotlib.pyplot as plt

wandb: WARNING W&B installed but not logged in. Run `wandb login` or set the WANDB_API_KEY env variable.
wandb: WARNING W&B installed but not logged in. Run `wandb login` or set the WANDB_API_KEY env variable.

Molecule Featurization using MATFeaturizer

MATFeaturizer is the featurizer intended to be used with the Molecular Attention Transformer, or MAT in short.
MATFeaturizer takes a smile string or molecule as input and returns a MATEncoding dataclass object, which contains 3
numpy arrays: Node features matrix, adjacency matrix and distance matrix.

featurizer = dc.feat.MATFeaturizer()
# Let us now take an example array of smile strings and featurize it.
smile_string = ["CCC"]
output = featurizer.featurize(smile_string)
print(type(output[0]))
print(output[0].node_features)
print(output[0].adjacency_matrix)
print(output[0].distance_matrix)

<class 'deepchem.feat.molecule_featurizers.mat_featurizer.MATEncoding'>
[[1. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.
0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0.]
[0. 0. 1. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1. 0. 0. 0. 0. 0. 0. 0. 1. 0. 0.
0. 0. 0. 0. 1. 0. 0. 0. 0. 0. 0. 0.]
[0. 0. 1. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1. 0. 0. 0. 0. 0. 0. 0. 1. 0. 0.
0. 0. 0. 0. 1. 0. 0. 0. 0. 0. 0. 0.]
[0. 0. 1. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 0. 1. 0. 0. 0. 0. 0. 1. 0. 0. 0.
0. 0. 0. 0. 1. 0. 0. 0. 0. 0. 0. 0.]]
[[0. 0. 0. 0.]
[0. 0. 0. 1.]
[0. 0. 0. 1.]
[0. 1. 1. 0.]]
[[1.e+06 1.e+06 1.e+06 1.e+06]
[1.e+06 0.e+00 2.e+00 1.e+00]
[1.e+06 2.e+00 0.e+00 1.e+00]
[1.e+06 1.e+00 1.e+00 0.e+00]]

Getting the Freesolv Hydration enthalpy dataset

We will now acquire the Freesolv Hydration enthalpy dataset from MoleculeNet. If it already exists in the directory, the
file will be used. Else, deepchem will automatically download the dataset from its AWS bucket.

tasks, dataset, transformers = dc.molnet.load_freesolv()

train_dataset, val_dataset, test_dataset = dataset
train_smiles = train_dataset.ids
val_smiles = val_dataset.ids

train_dataset

Training the model

Now that we have acquired the dataset to be used and made the necessary imports, we will be invoking the Molecular
Attention Transformer in deepchem, called MATModel, and we will be training it. We will be using default parameters for
the purposes of this tutorial, however they can be changed anytime according to the user's preferences.

device = 'cpu'
model = MATModel(device = device)

losses, val_losses = [], []

%%time
max_epochs = 10

for epoch in range(max_epochs):

loss = model.fit(train_dataset, nb_epoch = 1, max_checkpoints_to_keep = 1, all_losses = losses)
metric = dc.metrics.Metric(dc.metrics.score_function.rms_score)
val_losses.append(model.evaluate(val_dataset, metrics = [metric])['rms_score']**2)

# The warnings are not relevant to this tutorial thus we can safely skip them.

/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a

tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
node_features = torch.tensor(data[0]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:166: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
adjacency_matrix = torch.tensor(data[1]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:167: UserWarning: To copy construct from a
tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_(T
rue), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(data[2]).float()
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:171: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
torch.sum(torch.tensor(adj_matrix), dim=-1).unsqueeze(2) + eps)
/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/layers.py:178: UserWarning: To copy construct from
a tensor, it is recommended to use sourceTensor.clone().detach() or sourceTensor.clone().detach().requires_grad_
(True), rather than torch.tensor(sourceTensor).
distance_matrix = torch.tensor(distance_matrix).squeeze().masked_fill(
CPU times: user 20min 48s, sys: 10.7 s, total: 20min 58s
Wall time: 2min 41s

f, ax = plt.subplots()
ax.scatter(range(len(losses)), losses, label='train loss')
ax.scatter(range(len(val_losses)), val_losses, label='val loss')
plt.legend(loc='upper right');
Testing the model
Optimally, MAT should be trained for a lot more epochs with a GPU. Due to computational constraints, we train this
model for very few epochs in this tutorial. Let us now see how to predict the hydration enthalpy values for molecues
now with MAT.

# We will be predicting the enthalpy value for the smile string we featurized earlier in the MATFeaturizer section.
model.predict_on_batch(output)

/home/atreyamaj/Desktop/deepchem/deepchem/models/torch_models/mat.py:165: UserWarning: To copy construct from a

The architecture consits of 3 main sections: a generator, a discriminator, and a reward network.

The generator takes a sample (z) from a standard normal distribution to generate an a graph using a MLP (this limits the
network to a fixed maximum size) to generate the graph at once. Sepcifically a dense adjacency tensor A (bond types)
and an annotation matrix X (atom types) are produced. Since these are probabilities, a discrete, sparse x and a are
generated through categorical sampling.

The discriminator and reward network have the same architectures and recieve graphs as inputs. A Relational-GCN and
MLPs are used to produce the singular output.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands.

!pip install --pre deepchem

import deepchem
deepchem.__version__

Requirement already satisfied: deepchem in /usr/local/lib/python3.10/dist-packages (2.8.1.dev20240603202041)

Requirement already satisfied: joblib in /usr/local/lib/python3.10/dist-packages (from deepchem) (1.4.2)
Requirement already satisfied: numpy>=1.21 in /usr/local/lib/python3.10/dist-packages (from deepchem) (1.25.2)
Requirement already satisfied: pandas in /usr/local/lib/python3.10/dist-packages (from deepchem) (2.0.3)
Requirement already satisfied: scikit-learn in /usr/local/lib/python3.10/dist-packages (from deepchem) (1.2.2)
Requirement already satisfied: sympy in /usr/local/lib/python3.10/dist-packages (from deepchem) (1.12.1)
Requirement already satisfied: scipy>=1.10.1 in /usr/local/lib/python3.10/dist-packages (from deepchem) (1.11.4)
Requirement already satisfied: rdkit in /usr/local/lib/python3.10/dist-packages (from deepchem) (2023.9.6)
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eepchem) (2.8.2)
Requirement already satisfied: pytz>=2020.1 in /usr/local/lib/python3.10/dist-packages (from pandas->deepchem) (
2023.4)
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(2024.1)
Requirement already satisfied: Pillow in /usr/local/lib/python3.10/dist-packages (from rdkit->deepchem) (9.4.0)
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n->deepchem) (3.5.0)
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chem) (1.3.0)
Requirement already satisfied: six>=1.5 in /usr/local/lib/python3.10/dist-packages (from python-dateutil>=2.8.2-
>pandas->deepchem) (1.16.0)
WARNING:deepchem.feat.molecule_featurizers.rdkit_descriptors:No normalization for SPS. Feature removed!
WARNING:deepchem.feat.molecule_featurizers.rdkit_descriptors:No normalization for AvgIpc. Feature removed!
WARNING:tensorflow:From /usr/local/lib/python3.10/dist-packages/tensorflow/python/util/deprecation.py:588: calli
ng function (from tensorflow.python.eager.polymorphic_function.polymorphic_function) with experimental_relax_sha
pes is deprecated and will be removed in a future version.
Instructions for updating:
experimental_relax_shapes is deprecated, use reduce_retracing instead
WARNING:deepchem.models.torch_models:Skipped loading modules with pytorch-geometric dependency, missing a depend
ency. No module named 'torch_geometric'
WARNING:deepchem.models:Skipped loading modules with pytorch-geometric dependency, missing a dependency. cannot
import name 'DMPNN' from 'deepchem.models.torch_models' (/usr/local/lib/python3.10/dist-packages/deepchem/models
/torch_models/__init__.py)
WARNING:deepchem.models:Skipped loading modules with pytorch-lightning dependency, missing a dependency. No modu
le named 'lightning'
WARNING:deepchem.models:Skipped loading some Jax models, missing a dependency. No module named 'haiku'
'2.8.1.dev'

Import the packages you'll need.

import numpy as np
import matplotlib.pyplot as plt
import pandas as pd
import os
from collections import OrderedDict

import deepchem as dc
import deepchem.models
import torch
from deepchem.models.torch_models import BasicMolGANModel as MolGAN
from deepchem.models.optimizers import ExponentialDecay
from torch.nn.functional import one_hot
from rdkit import Chem
from rdkit.Chem.Draw import IPythonConsole
from rdkit.Chem import Draw

from deepchem.feat.molecule_featurizers.molgan_featurizer import GraphMatrix

Download, load, and extract the SMILES strings from the tox21 dataset. The original paper used the QM9 dataset,
however we use the tox21 dataset here to save time.

# Download from MolNet

# Try tox21 or LIPO dataset
tasks, datasets, transformers = dc.molnet.load_tox21()
df = pd.DataFrame(data={'smiles': datasets[0].ids})

Specify the maximum number of atoms to enocde for the featurizer and the MolGAN network. The higher the number of
atoms, the more data you'll have in the dataset. However, this also increases the model complexity as the input
dimensions become higher.

num_atoms = 12

smiles

0 CC(O)(P(=O)(O)O)P(=O)(O)O

1 CC(C)(C)OOC(C)(C)CCC(C)(C)OOC(C)(C)C

2 OC[C@H](O)[C@@H](O)[C@H](O)CO

3 CCCCCCCC(=O)[O-].CCCCCCCC(=O)[O-].[Zn+2]

4 CC(C)COC(=O)C(C)C

... ...

6259 CC1CCCCN1CCCOC(=O)c1ccc(OC2CCCCC2)cc1

6260 Cc1cc(CCCOc2c(C)cc(-c3noc(C(F)(F)F)n3)cc2C)on1

6261 O=C1OC(OC(=O)c2cccnc2Nc2cccc(C(F)(F)F)c2)c2ccc...

6262 CC(=O)C1(C)CC2=C(CCCC2(C)C)CC1C

6263 CC(C)CCC[C@@H](C)[C@H]1CC(=O)C2=C3CC[C@H]4C[C@...

6264 rows × 1 columns

Uncomment the first line if you want to subsample from the full dataset.
#data = df[['smiles']].sample(4000, random_state=42)
data = df

Initialize the featurizer with the maxmimum number of atoms per molecule. atom_labels is a parameter to pass the
atomic number of atoms you want to be able to parse. Similar to the num_atoms parameter above, more atom_labels
means more data, though the model gets more complex/unstable.

# create featurizer
feat = dc.feat.MolGanFeaturizer(max_atom_count=num_atoms, atom_labels=[0, 5, 6, 7, 8, 9, 11, 12, 13, 14]) #15, 16, 17

Extract the smiles from the dataframe as a list of strings

smiles = data['smiles'].values

Filter out the molecules with too many atoms to reduce the number of unnecessary error messages in later steps.

filtered_smiles = [x for x in smiles if Chem.MolFromSmiles(x).GetNumAtoms() < num_atoms]

[13:29:08] WARNING: not removing hydrogen atom without neighbors

The next cell featurizes the filtered molecules, however, since we have limited the atomic numbers to [5, 6, 7, 8,
9, 11, 12, 13, 14] which is B, C, N, O, F, Na, Mg, Al and Si, the featurizer fails to featurize several molecules in the
dataset. Feel free to experiment with more atomic numbers!

# featurize molecules
features = feat.featurize(filtered_smiles)

WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 0, CC(O)(P(=O)(O)O)P(=O)(O)O. Appending empty a

rray
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 11, O=[N+]([O-])[O-].O=[N+]([O-])[O-].[Ca+2]. A
ppending empty array
WARNING:deepchem.feat.base_classes:Exception message: 20
[13:29:09] WARNING: not removing hydrogen atom without neighbors
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 12, F[B-](F)(F)F.[H+]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 1
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 14, [I-].[K+]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 19
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 17, C=CC(=O)OCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 25, ClCOCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 27, [Cu]I. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 29
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 32, BrCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 33, CCC(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 39, NC(=S)NNC(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 40, NC(=S)C(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 41, C[Hg]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 42, [Hg+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 80
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 44, O=[Cr](=O)([O-])O[Cr](=O)(=O)[O-]. Appendin
g empty array
WARNING:deepchem.feat.base_classes:Exception message: 24
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 45, O=P(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 49, O=C(O)[C@@H](S)[C@H](S)C(=O)O. Appending em
pty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 54, CO[Si](CCCS)(OC)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 55, C[N+](C)=CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 57, O=[Zr](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 61, CC(C)OS(C)(=O)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 66, CC(Cl)(Cl)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 67, O=C(CCl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 68, CC(=O)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 71, ClCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 75, CCOP(=O)(CC)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 81, CSCCC=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 82, CC(C)(C)C(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 87, CNC(=O)NC(O)C(Cl)(Cl)Cl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 90, BrCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 91, O=S(=O)([O-])[O-].[Na+].[Na+]. Appending em
pty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 98, [O-][Cl+3]([O-])([O-])[O-]. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 106, OCCSSCCO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 107, ClCCCCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 108, [Ba+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 56
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 116, N#CSCSC#N. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 117, CCCCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 118, C[S+](C)CCC(N)C(=O)O. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 120, CC[Sn](Br)(CC)CC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 122, CCOP(=O)(OCC)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 133, CCOP(=O)([O-])C(N)=O. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 136, COC(=O)CCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 141, CCCCCCCCC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 142, COC(=O)C(Cl)C(=O)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 146, NCCOS(=O)(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 147, COP(=O)(OC)OC=C(Cl)Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 148, CC(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 151, Cl[Pd]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 152, ClC=CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 153, O=S(=O)([O-])CCCS(=O)(=O)[O-]. Appending e
mpty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 154, [TlH2+]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 81
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 155, CC(C)OP(C)(=O)OC(C)C. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 156, COS(=O)(=O)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 158, O=P([O-])([O-])OC(CO)CO. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 160, C=C(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 161, OC(CCl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 162, Cl[Ba]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 163, O=C(O)CP(=O)(O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 166, ClC(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 167, ClC(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 168, CC(C)(CCl)C(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 175, ClC(Cl)=C(Cl)C(Cl)=C(Cl)Cl. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 180, ClC(Cl)(Cl)C(Cl)(Cl)Cl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 183, [Na]I. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 185, BrCCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 187, CCNC(=S)NCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 190, CC(C)(C)S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 193, Cl/C=C/Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 194, Cl/C=C\Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 195, OCC(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 200, O=[Mo](=O)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 42
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 201, CCOP(=S)(S)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 203, O=[Cr]O[Cr]=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 24
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 204, [Cr+3]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 24
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 210, CCN(CC)C(=S)[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 211, C[Sn](C)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 212, CCCCC(CC)C(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 214, OCC(O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 217, O=S(=O)(O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 218, [Fe+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 26
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 223, N#C[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 224, CC(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 228, ClC(Cl)(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 230, CSCCCN=C=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 238, CCCC[Sn](Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 50
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 241, C=CCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 242, C=CCSSCCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 243, C=CCNC(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 245, Cl[Nd](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 246, [Co+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 27
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 250, CC(C)C(Br)C(=O)NC(N)=O. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 251, O=S(=O)([O-])CO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 253, CC(=O)C(Cl)C(=O)N(C)C. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 259, O=C/C(Cl)=C(/Cl)C(=O)O. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 260, O=C(O)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 263, C=CCSSCC=C. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 267, Cl[Yb](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 271, NS(=O)(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 272, [PbH2+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 82
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 276, OCC(S)CS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 279, CCCCNP(N)(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 281, N[C@@H](CS)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 282, CC(C)(O)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 284, NC(CS)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 290, ClCCN(CCCl)CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 291, O=C(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 293, [Fe+3]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 26
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 294, CCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 295, ClC(Cl)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 305, CC(=O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 310, [Cu+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 29
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 311, ClCC(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 316, Cl[In](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 322, [As]#[In]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 33
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 323, COS(=O)(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 332, O=S(=O)([O-])[O-].[Li+].[Li+]. Appending e
mpty array
WARNING:deepchem.feat.base_classes:Exception message: 3
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 333, CCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 334, CS(=O)(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 339, S=C([S-])NCCNC(=S)[S-]. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 341, C[N+]([O-])(CCCl)CCCl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 350, CCC(C)S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 355, O=C(O)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 356, FC(F)(Cl)C(F)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 357, BrC(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 360, COP(=O)(NC(C)=O)SC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 362, ClP(Cl)(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 370, OCC(CBr)(CBr)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 371, O=C(O)C(Cl)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 372, O=C(O)C(Cl)(Cl)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 374, OCCCCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 384, CSSC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 387, CC(Cl)(Cl)[N+](=O)[O-]. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 390, O=[N+]([O-])C(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 395, CNC(=S)NN. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 397, O=S(=O)(O)C(F)(F)F. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 400, CCSCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 401, CCCC[Sn](Cl)(Cl)CCCC. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 50
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 403, [C-]#N.[Cu+]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 29
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 404, CC(C)(C)C(=O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 405, CC(S)C(=O)NCC(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 406, [Cd+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 48
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 409, CC(CC(=O)Cl)CC(C)(C)C. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 411, CCCCCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 413, C[N+](C)(C)CC(O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 417, CNC(=S)[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 418, [SnH2+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 50
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 420, COC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 422, C=CC(Cl)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 423, O=[Se]([O-])[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 34
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 424, CCOC(=S)[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 429, Cl[Au](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 436, N#CCCC(Br)(C#N)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 440, C=CC(=O)[O-].C=CC(=O)[O-].[Zn+2]. Appendin
g empty array
WARNING:deepchem.feat.base_classes:Exception message: 30
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 441, CCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 442, OCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 444, CCCCCCI. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 445, CCOC(=O)CS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 448, CC(C)S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 449, COP(OC)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 450, C[Se]CC[C@H](N)C(=O)O. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 34
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 454, CN(C)C(=S)SC(=S)N(C)C. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 455, OC[P+](CO)(CO)CO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 457, CCOS(C)(=O)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 458, COP(=O)(O)OP(=O)(O)OC. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 463, OCC(Br)=C(Br)CO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 464, BrC/C=C/CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 465, N#CC(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 467, O=S(=O)([O-])CCO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 471, COP(=O)(O)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 473, Cl[Dy](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 474, CCCSSCCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 477, N#CC(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 478, NC(=O)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 479, CC(=O)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 481, CCCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 487, OC(O)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 491, ClC(Cl)=C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 492, ClC(Cl)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 493, ClCC(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 495, OCCSCSCCO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 497, CC(=O)[O-].[K+]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 19
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 498, O=C(Cl)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 501, CCSC(=O)N(CC)CC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 504, ClCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 506, CC(Br)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 507, S=C([S-])NCCNC(=S)[S-].[Mn+2]. Appending e
mpty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 511, COS(=O)(=O)C(F)(F)F. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 515, O=C(O)C(Br)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 516, O=C([O-])CS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 518, O=S(=O)([O-])SSS(=O)(=O)[O-]. Appending em
pty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 520, BrCC(Br)(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 521, BrC(Br)C(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 523, CS(C)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 532, CNC(=S)N(C)C. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 534, CSC(C)(C)/C=N\O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 535, N#CCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 536, ClCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 537, O=C([O-])C(=O)[O-].[Ca+2]. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 20
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 539, Br[Ca]Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 543, CN(C)C(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 544, C#CC(O)(/C=C\Cl)CC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 545, BrCCCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 546, O=P([O-])(O)C(Cl)(Cl)P(=O)([O-])O. Appendi
ng empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 548, CCOP(OCC)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 551, CCCCCCC(C)(C)S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 559, CC(CCl)OC(C)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 560, OCC(CO)(CBr)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 561, ClCCOCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 563, OCCSCCO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 564, P#[In]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 565, O=C(O)CC(Cl)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 566, N#CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 567, [Mn+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 25
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 568, CCC(C)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 571, FC(F)OC(Cl)C(F)(F)F. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 576, CC(O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 578, O=C([O-])[O-].[Sr+2]. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 38
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 583, CNC(=S)NC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 586, ClCCOCCOCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 588, CC(C)(C)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 593, N#CC(Br)(Br)C(N)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 597, CCCC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 598, CCCCCCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 599, CC(Cl)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 600, O=C(O)CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 601, O=[Cd]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 48
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 604, S=C=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 608, ClC(Cl)(Cl)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 611, O=S(=O)([O-])CCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 613, OCC(O)CS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 614, [Be+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 4
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 615, CC(C)(C)C(=O)C(Cl)Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 617, O=S(=O)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 618, O=S(=O)([O-])[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 621, O=C([O-])CC(S[Au])C(=O)[O-]. Appending emp
ty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 629, CN(C)CCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 637, O=P(O)(O)CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 638, N#CC(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 639, NC(=O)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 640, CC(Cl)C(C)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 644, CC=C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 648, CC(=O)N[C@@H](CS)C(=O)O. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 650, [Zn+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 30
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 651, O=C(O)C(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 653, O=C([O-])P(=O)([O-])[O-]. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 654, C=CS(=O)(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 660, CCCCCCCCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 666, O=S(=O)([O-])O.[Na+]. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 668, ClSC(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 671, N[Pt](N)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 678, CCCCSCCCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 681, COS(C)(=O)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 686, O=C(O)CS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 688, NCCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 692, CN(C)P(=O)(N(C)C)N(C)C. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 694, CC(C)OC(=S)[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 695, CNC(=O)ON=C(C)SC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 698, CCOC(=O)CC(=O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 699, BrC(Br)C(Br)(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 700, CCOC(=O)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 702, O=[Se](O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 34
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 703, NC(N)=[Se]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 34
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 704, CCOS(=O)(=O)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 707, C=C(C)CS(=O)(=O)[O-]. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 708, CCCCOC(=O)CCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 712, CNCCS(=O)(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 713, FC(F)(F)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 715, CCSCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 716, ClCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 718, OCC(Br)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 721, C[Si](C)(C)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 722, O=[N+]([O-])C(Cl)(Cl)Cl. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 724, O=C([O-])CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 728, CCCCCSCCCCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 729, CC(S)C(C)S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 732, O=[Se]=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 34
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 733, ClC/C=C\CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 735, COC(=O)CS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 737, ClCC(Br)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 738, BrCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 740, IC(I)=C(I)I. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 741, O=P([O-])([O-])OP(=O)([O-])[O-]. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 742, CCCCCCCCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 743, N#CCCSCCC#N. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 745, CC(Cl)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 748, CC(C)(Cl)[N+](=O)[O-]. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 749, CCC(Cl)[N+](=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 751, N#CSCC(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 755, CCN(CC)CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 757, C=CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 758, C=CCN=C=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 761, O=S([O-])CO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 762, CCSC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 764, CCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 765, OCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 767, C=CCOCC(O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 770, C/C(Cl)=C/CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 771, BrCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 773, O=S(=O)([O-])OOS(=O)(=O)[O-]. Appending em
pty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 774, O=[N+]([O-])[O-].[K+]. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 19
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 778, CS(=O)(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 780, Cl[Zn]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 781, ClC/C=C/CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 782, CC(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 783, ClCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 786, NC(=S)NC(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 788, CC(Cl)(Cl)C(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 790, C[Sn](Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 791, C=CCS(=O)(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 792, O=P([O-])(O)OP(=O)([O-])O. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 799, CN(CCCl)CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 800, C=C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 801, N=C(N)S(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 803, COP(=O)(OC)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 810, Cl[Ni]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 812, CCOP(=S)(Cl)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 813, COP(=S)(Cl)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 814, Cl[Sb](Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 823, O=[Bi]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 824, [Br-].[Na+]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 839, N[C@@H](CSCCCO)C(=O)O. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 843, O=C(C(Cl)(Cl)Cl)C(Cl)(Cl)Cl. Appending emp
ty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 849, II. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 853, O=C([O-])C(Cl)(Cl)Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 857, O=C(CCl)NCO. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 858, SCCCCCCCCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 861, O=C(Cl)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 863, COC(=O)C(Br)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 864, ClC=C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 865, ClCC(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 866, CC(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 867, FC(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 873, ClCC=CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 877, CCOC(=O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 879, O=S(=O)([O-])CC(S)CS. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 880, O=[N+]([O-])C(Br)(CO)CO. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 881, OCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 888, SCCSCCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 889, CCCCNC(C)(C)[PH](=O)O. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 892, CCCCCCCCSCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 893, O=S(O)CO[Na]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 901, COP(C)(=O)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 906, [Ca+2].[Cl-].[Cl-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 911, CCCCCCCCCI. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 918, CC(C)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 919, [SbH6+3]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 51
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 920, ClC(Cl)C(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 924, O=P(O)(O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 927, NC(CSCC(=O)O)C(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 935, [Ni+2]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 28
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 940, O=[N+]([O-])O[Cd]O[N+](=O)[O-]. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 48
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 941, CCOC(=O)C(Cl)C(C)=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 943, N[C@@H](COP(=O)(O)O)C(=O)O. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 947, NNC(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 948, CCCCS(=O)(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 949, NC(N)=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 952, CCOC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 953, NS(=O)(=O)[O-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 954, COCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 955, C[N+](C)(C)CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 956, CCOP(=S)(OCC)SCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 958, CC[Ge](Cl)(CC)CC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 960, CCOP(=O)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 967, O=C(O)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 968, CCC(C)SSC(C)CC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 970, O=CC(Br)(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 971, O=C(O)C(Br)(Br)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 978, C=C(C)CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 979, CCCCCCCCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 981, CCCCC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 982, CCC(C)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 983, N#CCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 984, O=C(O)CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 985, O=S(=O)(O)F. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 986, O=C(Cl)/C=C/C(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 987, O=C(O)CCSCCC(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 989, FC(F)(F)C(Cl)Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 991, O=C(O)CCS. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 997, CO[PH](=O)OC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1003, CC(C)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1008, O=C(CCl)C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1009, N#C[Au-]C#N. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 79
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1010, ClC(Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1013, CCCSC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1017, ClC=CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1018, NCCS(=O)(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1020, CCOP(O)OCC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1022, FC(Cl)(Cl)C(F)(Cl)Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1024, CN(C)C(=S)[S-]. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1027, ClCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1028, CCCCCCCCCBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1029, Cl[Sn](Cl)(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1030, CC(O)(P(=O)([O-])O)P(=O)([O-])O. Appendin
g empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1041, CN=C=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1043, ClCCOCOCCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1044, CC(C)=CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1046, C[As](C)(=O)O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 33
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1049, COP(N)(=O)SC. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1053, O=S(=O)([O-])CC(O)CCl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1054, CC(C)CP(=S)([S-])CC(C)C. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1060, O=C([O-])C(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1061, NNC(=S)NN. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1065, O=CCCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1067, CCCCCCCC(=O)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1070, NC(=O)CI. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1071, IC(I)I. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1073, FC(F)OC(F)(F)C(F)Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1074, O=S(=O)(Cl)c1ccccc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1077, Nc1ccccc1S(=O)(=O)O. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1087, ClCc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1090, Nc1cc(Cl)cc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1093, ClCc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1094, COc1cccc(Br)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1099, Cc1cc(O)cc(C)c1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1100, S=C=NCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1101, ClCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1107, O=C=Nc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1109, O=Cc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1111, O=Cc1cccc(Br)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1117, O=C(CBr)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1120, Cc1cc(C)c(N)c(Cl)c1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1122, NC(=S)Nc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1127, O=C(Cl)c1cc(Cl)cc(Cl)c1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1128, COC(=O)c1cccc(Cl)c1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1129, O=[N+]([O-])c1ccc(Cl)cc1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1135, [S-]c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1137, O=[N+]([O-])c1cccc(Cl)c1Cl. Appending emp
ty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1138, O=[N+]([O-])c1ccc(Cl)cc1Cl. Appending emp
ty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1139, O=[N+]([O-])c1ccc(Cl)c(Cl)c1. Appending e
mpty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1140, Oc1ccc(Cl)c(Cl)c1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1141, Oc1cc(Cl)cc(Cl)c1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1142, Oc1c(Cl)ccc(Cl)c1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1143, ClC(Cl)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1146, O=C(Cl)OCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1151, BrCCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1153, Cc1c(Cl)cccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1159, Cc1ccccc1CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1164, Nc1ccc(Cl)cc1[N+](=O)[O-]. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1167, Oc1cccc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1170, Cc1c(N)cccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1171, Cc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1172, Nc1ccc(Br)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1177, NC(=S)c1c(Cl)cccc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1178, Cc1ccccc1Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1184, BrCCOc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1185, Brc1ccc(Br)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1191, CCc1ccc(Br)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1196, Cc1ccccc1S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1199, O=S(=O)([O-])c1ccc(O)cc1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1205, Nc1cc(Cl)c(N)c(Cl)c1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1206, Oc1cc(Cl)c(Cl)cc1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1210, O=[N+]([O-])c1ccccc1CCl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1211, O=[N+]([O-])c1ccc(CCl)cc1. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1212, O=[N+]([O-])c1cccc(CCl)c1. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1213, Nc1ccc(S(=O)(=O)[O-])cc1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1221, CC(=O)O[Hg]c1ccccc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 80
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1222, NC(=O)c1c(Cl)cccc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1223, Fc1cccc(Cl)c1CCl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1231, O=C(CCl)Nc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1232, COc1ccc(OC)c(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1233, Cc1cc(O)c(Cl)cc1C. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1237, O=C(Cl)c1c(Cl)cccc1Cl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1241, Cc1ccc(S(=O)(=O)O)cc1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1246, ICCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1247, O=[N+]([O-])c1cccc(I)c1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1248, Nc1c(Cl)cc(Cl)cc1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1249, Nc1cc(Cl)ccc1O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1250, O=Cc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1251, N#Cc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1252, COC(=O)c1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1255, N#CSCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1260, O=P(O)(O)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1263, Clc1ccc(Cl)c(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1274, O=[N+]([O-])c1ccc(CBr)cc1. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1275, Cc1ccc(Br)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1277, COc1ccc(Br)c(C)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1278, Oc1c(Cl)c(Cl)cc(Cl)c1Cl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1287, C=Cc1cccc(CCl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1288, Cc1cc(O)c(Cl)c(C)c1Cl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1290, Cc1ccc(S(N)(=O)=O)cc1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1291, CCC(=O)c1ccc(Cl)cc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1293, CC(C)(C)c1ccc(S)cc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1294, O=C(CS)Nc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1306, Nc1cc(Cl)ccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1307, Nc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1308, O=[PH](O)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1313, O=C(CBr)c1ccc(O)cc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1314, FC(F)(F)c1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1315, O=C(O)c1cccc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1316, O=C(O)c1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1317, O=C(O)c1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1318, FC(F)(F)c1cccc(Cl)c1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1322, Cc1ccccc1S(=O)(=O)[O-]. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1324, O=Cc1cc(O)ccc1Br. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1326, Clc1ccc(C(Cl)(Cl)Cl)cc1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1328, Cc1cc(Cl)c(C)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1329, Clc1ccc(Cl)c(Cl)c1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1330, [O-]c1cc(Cl)c(Cl)cc1Cl. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1332, COc1cc(Cl)ccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1333, CSc1ccc(C=O)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1338, Cc1ccc(Cl)c(O)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1344, Cc1cc(O)ccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1345, Oc1c(Cl)cc(Cl)c(Cl)c1Cl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1347, COc1ccc(Cl)cc1C. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1348, Cc1cc(Cl)ccc1N. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1351, Cc1ccc(Cl)cc1N. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1352, Cc1ccc(N)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1353, Nc1ccc(N)c(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1354, Nc1ccc(Cl)cc1N. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1355, Nc1ccc(Cl)c(N)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1356, O=[N+]([O-])c1ccccc1Cl. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1359, O=S(=O)(O)c1ccccc1O. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1361, N#Cc1c(Cl)cccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1363, ClC(Cl)(Cl)c1ccccc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1367, Sc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1368, Nc1cc(Cl)c(O)c(Cl)c1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1369, O=C(O)c1ccc([Hg]Cl)cc1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1370, Oc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1374, SCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1379, Oc1cc(Cl)c(Cl)c(Cl)c1Cl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1380, Nc1cc(C(=O)O)ccc1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1381, N#CCc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1383, Cc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1384, Oc1cc(O)c(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1391, Oc1ccccc1[Hg]Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 80
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1394, O=S(=O)(O)c1ccc(Cl)cc1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1395, O=C(O)c1cc(Cl)cc(Cl)c1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1396, O=C(O)c1ccc(Cl)c(Cl)c1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1398, Clc1c(Cl)cc(Cl)c(Cl)c1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1402, Oc1ccc(Cl)c(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1403, Oc1c(Cl)cccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1405, Oc1cc(Cl)cc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1406, Oc1cccc(Cl)c1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1407, Clc1cccc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1408, Oc1cc(Cl)ccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1411, CC(C)(CCl)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1419, Nc1ccc([As](=O)([O-])O)cc1. Appending emp
ty array
WARNING:deepchem.feat.base_classes:Exception message: 33
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1421, O=Cc1ccc(F)c(Br)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1422, O=C(O)c1ccccc1S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1423, O=P(O)(O)Oc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1429, Oc1cc(Cl)c(Cl)c(Cl)c1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1436, Nc1ccc(Cl)c(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1437, Nc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1438, FC(F)(F)c1ccc(Cl)cc1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1440, Nc1ccc([As](=O)(O)O)cc1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 33
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1443, OCCSc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1446, O=S(=O)(O)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1450, Sc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1451, ClCc1cccc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1453, Fc1cc(Br)ccc1CBr. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1455, Oc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1457, Cc1c(Cl)cccc1[N+](=O)[O-]. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1460, Cc1cc(Cl)ccc1O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1462, Clc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1463, Clc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1464, Oc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1465, Brc1ccc(Br)c(Br)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1471, N#Cc1cc(Br)c(O)c(Br)c1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1472, N#Cc1cc(I)c(O)c(I)c1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 53
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1477, O=S(=O)(O)c1ccc(O)cc1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1480, Clc1cc(Cl)cc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1481, Clc1cccc(Cl)c1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1483, Clc1cc(Cl)c(Cl)c(Cl)c1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1484, Nc1ccc(S(N)(=O)=O)cc1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1487, Nc1cccc(S(=O)(=O)O)c1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1493, Brc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1498, Oc1c(Br)cc(Br)cc1Br. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1499, Oc1ccc([Hg]Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1500, Oc1c(Cl)cc(Cl)cc1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1501, O=C(Cl)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1508, Clc1cc(Cl)c(Cl)c(Cl)c1Cl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1509, Cc1cccc(Br)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1510, BrCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1513, O=[N+]([O-])c1cccc(Cl)c1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1517, Cl[Hg]c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1521, Cc1ccccc1S(N)(=O)=O. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1523, Cc1ccc(Cl)c(N)c1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1525, O=C(Cl)c1ccccc1F. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1530, Fc1ccc(Br)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1533, OCc1ccc(Cl)cc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1536, S=C=NCCc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1539, S=C=Nc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1541, Cc1ccc(S)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1542, CCCCc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1562, ClP(Cl)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1571, O=Cc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1572, Nc1cccc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1580, CCC(=O)c1cccc(Cl)c1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1581, O=[N+]([O-])c1ccc(F)c(Cl)c1. Appending em
pty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1585, OB(O)O[Hg]c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 80
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1588, BrCc1ccc(Br)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1589, O=C(O)c1cc(Cl)ccc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1590, O=C(O)c1c(Cl)cccc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1591, O=C(O)c1cccc(Cl)c1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1592, O=C(O)c1ccc(Cl)cc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1593, O=Cc1c(Cl)cccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1594, O=Cc1ccc(Cl)c(Cl)c1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1595, O=C(Cl)c1ccc(F)c(Cl)c1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1598, Cc1ccc([N+](=O)[O-])cc1Cl. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1599, Cc1cccc(Cl)c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1600, NS(=O)(=O)c1ccccc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1603, O=C=Nc1ccc(Cl)c(Cl)c1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1605, NC(=O)Nc1ccc(Cl)cc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1607, O=C(CCl)c1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1608, Nc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1609, CSc1ccc(Cl)cc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1610, Cc1ccccc1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1611, CS(=O)(=O)c1ccc(Cl)cc1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1612, Clc1ccccc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1614, Oc1nc(Cl)c(Cl)cc1Cl. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1616, O=C(O)c1cccc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1619, Clc1ccccn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1620, ClCc1ccccn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1621, ClCc1cccnc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1626, Clc1nc(Cl)c(Cl)c(Cl)c1Cl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1629, Clc1cccc(C(Cl)(Cl)Cl)n1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1637, CCc1cc(C(N)=S)ccn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1643, Clc1ccc(C(Cl)(Cl)Cl)cn1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1648, Cc1nc(C)c(Cl)c(O)c1Cl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1649, O=C(O)c1nc(Cl)ccc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1659, Clc1cc(Cl)c(Cl)nc1Cl. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1665, Clc1cccc2ccccc12. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1668, Clc1ccc2ccccc2c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1674, O=S(=O)(O)NC1CCCCC1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1683, SC1CCCCC1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1694, O=S(=O)([O-])NC1CCCCC1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1706, CCn1cc[n+](C)c1.N#C[S-]. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1729, [O-][n+]1ccccc1[S-]. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1740, [O-][n+]1ccc(Cl)cc1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1748, Nc1nc(N)nc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1750, Clc1nc(Cl)nc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1751, CCNc1nc(N)nc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1754, CC(C)SCc1ccco1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1758, Cc1c(S)cco1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1759, CSSc1c(C)occ1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1764, CC(=O)SCc1ccco1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1777, C[C@@H]1O[C@@H]1P(=O)([O-])[O-]. Appendin
g empty array
WARNING:deepchem.feat.base_classes:Exception message: 15
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1781, BrCC1CO1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1784, ClCC1CO1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1787, Cc1nc2ccccc2s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1788, Nc1nc2c(Cl)cccc2s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1789, Sc1nc2ccccc2s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1790, [S-]c1nc2ccccc2s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1791, c1ccc2scnc2c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1792, Nc1nc2ccccc2s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1793, Brc1nc2ccccc2s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1794, Cc1cccc2c1nc(N)s2. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1795, Nc1nc(Cl)cc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1796, Clc1cc(Cl)nc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1797, Clc1ccnc(Cl)n1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1808, Cc1c(CCCl)scn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1809, Cc1cscn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1810, CC(C)Cc1nccs1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1811, Nc1nc(CC(=O)O)cs1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1812, Nc1nccs1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1813, CC(=O)c1nccs1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1814, Nc1ncc([N+](=O)[O-])s1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1815, Cc1c(CCO)scn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1816, CCCc1ncc(C(=O)O)s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1817, CC(=O)c1c(C)nc(C)s1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1849, Cc1nc2ccc(Cl)cc2[nH]1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1870, O=C1CCCCC1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1892, CSc1cnccn1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1896, ClCCN1CCCC1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1902, CC1(C)C(=O)N(Cl)C(=O)N1Br. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1903, CC1(C)C(=O)N(Br)C(=O)N1Cl. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1905, CC1(C)C(=O)N(Br)C(=O)N1Br. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1906, CC1(C)C(=O)N(Cl)C(=O)N1Cl. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1920, SC1CCCC1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1924, O=C1OC(O)C(C(Cl)Cl)=C1Cl. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1925, Clc1c(Cl)c(Cl)c(Cl)s1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1926, c1cscc1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1927, Cc1ccc(C=O)s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1928, Cc1c(Br)ccs1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1933, O=c1[nH]c(=O)n(Cl)c(=O)n1Cl. Appending em
pty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1937, O=[N+]([O-])C1(Br)COCOC1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 35
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1952, Clc1ccc2[nH]nnc2c1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1954, Oc1ccc(Cl)c2c1CCC2. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1962, O=c1[nH]c2cc(Cl)ccc2o1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1963, O=c1[nH]c2ccc(Cl)cc2o1. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1974, [Fe+2].c1c[cH-]cc1.c1c[cH-]cc1. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 26
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1975, [Ni+2].c1c[cH-]cc1.c1c[cH-]cc1. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 28
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1976, [Cr+2].c1c[cH-]cc1.c1c[cH-]cc1. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 24
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1977, [Co+2].c1c[cH-]cc1.c1c[cH-]cc1. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 27
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1982, Cn1sccc1=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1983, Cn1sc(Cl)cc1=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1984, Cc1c[nH]c(=S)[nH]c1=O. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1985, Cc1cc(=O)[nH]c(=S)[nH]1. Appending empty
array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1986, O=c1cc[nH]c(=S)[nH]1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1987, CCCc1cc(=O)[nH]c(=S)[nH]1. Appending empt
y array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 1998, O=C1CCC(=O)N1Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2008, Cl[C@H]1OCCO[C@@H]1Cl. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2011, Sc1nnc(S)s1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2024, O=c1[nH]sc2ccccc12. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2025, O=c1[nH]sc2cc(Cl)ccc12. Appending empty a
rray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2033, Cn1cc[nH]c1=S. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2040, O=C1Cc2cc(Cl)ccc2N1. Appending empty arra
y
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2058, ClC1=C(Cl)C(Cl)(Cl)C(Cl)=C1Cl. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2061, C1CSCCS1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2062, CC1(O)CSC(C)(O)CS1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2063, O=S1(=O)CCCC1. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2064, O=S1(=O)CC(Cl)(Cl)C(Cl)(Cl)C1. Appending
empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2065, CC(=O)NC1CCSC1=O. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2069, S=C1NC=NC2N=CNC12. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2070, S=c1[nH]c2ccccc2[nH]1. Appending empty ar
ray
WARNING:deepchem.feat.base_classes:Exception message: 16
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2072, O=c1cc(O)c(Cl)c[nH]1. Appending empty arr
ay
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Failed to featurize datapoint 2079, ClC1=C(Cl)C1(Cl)Cl. Appending empty array
WARNING:deepchem.feat.base_classes:Exception message: 17
WARNING:deepchem.feat.base_classes:Exception message: setting an array element with a sequence. The requested ar
ray has an inhomogeneous shape after 1 dimensions. The detected shape was (2081,) + inhomogeneous part.

Remove more invalid molecules.

indices = [ i for i, data in enumerate(features) if type(data) is GraphMatrix ]

print(indices)
features = [features[i] for i in indices]
[1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 13, 15, 16, 18, 19, 20, 21, 22, 23, 24, 26, 28, 29, 30, 31, 34, 35, 36, 37, 38,
43, 46, 47, 48, 50, 51, 52, 53, 56, 58, 59, 60, 62, 63, 64, 65, 69, 70, 72, 73, 74, 76, 77, 78, 79, 80, 83, 84,
85, 86, 88, 89, 92, 93, 94, 95, 96, 97, 99, 100, 101, 102, 103, 104, 105, 109, 110, 111, 112, 113, 114, 115, 119
, 121, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 134, 135, 137, 138, 139, 140, 143, 144, 145, 149, 150,
157, 159, 164, 165, 169, 170, 171, 172, 173, 174, 176, 177, 179, 181, 182, 184, 186, 188, 189, 191, 192, 196, 19
7, 198, 199, 202, 205, 206, 207, 208, 209, 213, 215, 216, 219, 220, 221, 222, 225, 226, 227, 229, 231, 232, 233,
234, 235, 236, 237, 239, 240, 244, 247, 248, 249, 252, 254, 255, 256, 257, 258, 261, 262, 264, 265, 266, 268, 26
9, 270, 273, 274, 275, 277, 278, 280, 283, 285, 286, 287, 288, 289, 292, 296, 297, 298, 299, 300, 301, 302, 303,
304, 306, 307, 308, 309, 312, 313, 314, 315, 317, 318, 319, 320, 321, 324, 325, 326, 327, 328, 329, 330, 331, 33
5, 336, 337, 338, 340, 342, 343, 344, 345, 346, 347, 348, 349, 351, 352, 353, 354, 358, 359, 361, 363, 364, 365,
366, 367, 368, 369, 373, 375, 376, 377, 378, 379, 380, 381, 382, 383, 385, 386, 388, 389, 391, 392, 393, 394, 39
6, 398, 399, 402, 407, 408, 410, 412, 414, 415, 416, 419, 421, 425, 426, 427, 428, 430, 431, 432, 433, 434, 437,
438, 439, 443, 446, 447, 451, 452, 453, 456, 459, 460, 461, 462, 466, 468, 469, 470, 472, 475, 476, 480, 482, 48
3, 484, 485, 486, 488, 489, 490, 494, 499, 500, 502, 503, 505, 508, 509, 510, 512, 513, 514, 517, 519, 522, 524,
525, 526, 527, 528, 529, 530, 531, 533, 538, 540, 541, 542, 547, 549, 550, 552, 553, 554, 555, 556, 557, 558, 56
2, 569, 570, 572, 573, 574, 575, 577, 579, 580, 581, 582, 584, 585, 587, 589, 590, 591, 592, 594, 595, 596, 602,
603, 605, 606, 607, 609, 610, 612, 616, 619, 620, 622, 623, 624, 625, 626, 627, 628, 630, 631, 632, 633, 634, 63
5, 636, 641, 642, 643, 645, 646, 647, 649, 652, 655, 656, 657, 658, 659, 661, 662, 663, 664, 665, 667, 669, 670,
672, 673, 674, 675, 676, 677, 679, 680, 682, 683, 684, 687, 689, 690, 691, 693, 696, 697, 701, 705, 706, 709, 71
0, 711, 714, 717, 719, 720, 723, 725, 726, 727, 730, 731, 734, 736, 739, 744, 746, 747, 750, 752, 753, 754, 756,
759, 760, 763, 766, 768, 769, 772, 775, 776, 777, 779, 784, 785, 787, 789, 793, 794, 795, 796, 797, 798, 802, 80
4, 805, 806, 807, 808, 809, 811, 815, 816, 817, 818, 819, 820, 821, 822, 825, 826, 827, 828, 829, 830, 831, 832,
833, 834, 835, 836, 837, 838, 840, 841, 842, 844, 845, 846, 847, 848, 850, 851, 852, 854, 855, 856, 859, 860, 86
2, 868, 869, 870, 871, 872, 874, 875, 876, 878, 882, 883, 884, 885, 886, 887, 890, 891, 894, 895, 896, 897, 898,
899, 900, 902, 903, 904, 905, 907, 908, 909, 910, 912, 913, 914, 915, 916, 917, 921, 922, 923, 925, 926, 928, 92
9, 930, 931, 932, 933, 934, 936, 937, 938, 939, 942, 944, 945, 946, 950, 951, 957, 959, 961, 962, 963, 964, 965,
966, 969, 972, 973, 974, 975, 976, 977, 980, 988, 990, 992, 993, 994, 995, 996, 998, 999, 1000, 1001, 1002, 1004
, 1005, 1006, 1007, 1011, 1012, 1014, 1015, 1016, 1019, 1021, 1023, 1025, 1026, 1031, 1032, 1033, 1034, 1035, 10
36, 1037, 1038, 1039, 1040, 1042, 1045, 1047, 1048, 1050, 1051, 1052, 1055, 1056, 1057, 1058, 1059, 1062, 1063,
1064, 1066, 1068, 1069, 1072, 1075, 1076, 1078, 1079, 1080, 1081, 1082, 1083, 1084, 1085, 1086, 1088, 1089, 1091
, 1092, 1095, 1096, 1097, 1098, 1102, 1103, 1104, 1105, 1106, 1108, 1110, 1112, 1113, 1114, 1115, 1116, 1118, 11
19, 1121, 1123, 1124, 1125, 1126, 1130, 1131, 1132, 1133, 1134, 1136, 1144, 1145, 1147, 1148, 1149, 1150, 1152,
1154, 1155, 1156, 1157, 1158, 1160, 1161, 1162, 1163, 1165, 1166, 1168, 1169, 1173, 1174, 1175, 1176, 1179, 1180
, 1181, 1182, 1183, 1186, 1187, 1188, 1189, 1190, 1192, 1193, 1194, 1195, 1197, 1198, 1200, 1201, 1202, 1203, 12
04, 1207, 1208, 1209, 1214, 1215, 1216, 1217, 1218, 1219, 1220, 1224, 1225, 1226, 1227, 1228, 1229, 1230, 1234,
1235, 1236, 1238, 1239, 1240, 1242, 1243, 1244, 1245, 1253, 1254, 1256, 1257, 1258, 1259, 1261, 1262, 1264, 1265
, 1266, 1267, 1268, 1269, 1270, 1271, 1272, 1273, 1276, 1279, 1280, 1281, 1282, 1283, 1284, 1285, 1286, 1289, 12
92, 1295, 1296, 1297, 1298, 1299, 1300, 1301, 1302, 1303, 1304, 1305, 1309, 1310, 1311, 1312, 1319, 1320, 1321,
1323, 1325, 1327, 1331, 1334, 1335, 1336, 1337, 1339, 1340, 1341, 1342, 1343, 1346, 1349, 1350, 1357, 1358, 1360
, 1362, 1364, 1365, 1366, 1371, 1372, 1373, 1375, 1376, 1377, 1378, 1382, 1385, 1386, 1387, 1388, 1389, 1390, 13
92, 1393, 1397, 1399, 1400, 1401, 1404, 1409, 1410, 1412, 1413, 1414, 1415, 1416, 1417, 1418, 1420, 1424, 1425,
1426, 1427, 1428, 1430, 1431, 1432, 1433, 1434, 1435, 1439, 1441, 1442, 1444, 1445, 1447, 1448, 1449, 1452, 1454
, 1456, 1458, 1459, 1461, 1466, 1467, 1468, 1469, 1470, 1473, 1474, 1475, 1476, 1478, 1479, 1482, 1485, 1486, 14
88, 1489, 1490, 1491, 1492, 1494, 1495, 1496, 1497, 1502, 1503, 1504, 1505, 1506, 1507, 1511, 1512, 1514, 1515,
1516, 1518, 1519, 1520, 1522, 1524, 1526, 1527, 1528, 1529, 1531, 1532, 1534, 1535, 1537, 1538, 1540, 1543, 1544
, 1545, 1546, 1547, 1548, 1549, 1550, 1551, 1552, 1553, 1554, 1555, 1556, 1557, 1558, 1559, 1560, 1561, 1563, 15
64, 1565, 1566, 1567, 1568, 1569, 1570, 1573, 1574, 1575, 1576, 1577, 1578, 1579, 1582, 1583, 1584, 1586, 1587,
1596, 1597, 1601, 1602, 1604, 1606, 1613, 1615, 1617, 1618, 1622, 1623, 1624, 1625, 1627, 1628, 1630, 1631, 1632
, 1633, 1634, 1635, 1636, 1638, 1639, 1640, 1641, 1642, 1644, 1645, 1646, 1647, 1650, 1651, 1652, 1653, 1654, 16
55, 1656, 1657, 1658, 1660, 1661, 1662, 1663, 1664, 1666, 1667, 1669, 1670, 1671, 1672, 1673, 1675, 1676, 1677,
1678, 1679, 1680, 1681, 1682, 1684, 1685, 1686, 1687, 1688, 1689, 1690, 1691, 1692, 1693, 1695, 1696, 1697, 1698
, 1699, 1700, 1701, 1702, 1703, 1704, 1705, 1707, 1708, 1709, 1710, 1711, 1712, 1713, 1714, 1715, 1716, 1717, 17
18, 1719, 1720, 1721, 1722, 1723, 1724, 1725, 1726, 1727, 1728, 1730, 1731, 1732, 1733, 1734, 1735, 1736, 1737,
1738, 1739, 1741, 1742, 1743, 1744, 1745, 1746, 1747, 1749, 1752, 1753, 1755, 1756, 1757, 1760, 1761, 1762, 1763
, 1765, 1766, 1767, 1768, 1769, 1770, 1771, 1772, 1773, 1774, 1775, 1776, 1778, 1779, 1780, 1782, 1783, 1785, 17
86, 1798, 1799, 1800, 1801, 1802, 1803, 1804, 1805, 1806, 1807, 1818, 1819, 1820, 1821, 1822, 1823, 1824, 1825,
1826, 1827, 1828, 1829, 1830, 1831, 1832, 1833, 1834, 1835, 1836, 1837, 1838, 1839, 1840, 1841, 1842, 1843, 1844
, 1845, 1846, 1847, 1848, 1850, 1851, 1852, 1853, 1854, 1855, 1856, 1857, 1858, 1859, 1860, 1861, 1862, 1863, 18
64, 1865, 1866, 1867, 1868, 1869, 1871, 1872, 1873, 1874, 1875, 1876, 1877, 1878, 1879, 1880, 1881, 1882, 1883,
1884, 1885, 1886, 1887, 1888, 1889, 1890, 1891, 1893, 1894, 1895, 1897, 1898, 1899, 1900, 1901, 1904, 1907, 1908
, 1909, 1910, 1911, 1912, 1913, 1914, 1915, 1916, 1917, 1918, 1919, 1921, 1922, 1923, 1929, 1930, 1931, 1932, 19
34, 1935, 1936, 1938, 1939, 1940, 1941, 1942, 1943, 1944, 1945, 1946, 1947, 1948, 1949, 1950, 1951, 1953, 1955,
1956, 1957, 1958, 1959, 1960, 1961, 1964, 1965, 1966, 1967, 1968, 1969, 1970, 1971, 1972, 1973, 1978, 1979, 1980
, 1981, 1988, 1989, 1990, 1991, 1992, 1993, 1994, 1995, 1996, 1997, 1999, 2000, 2001, 2002, 2003, 2004, 2005, 20
06, 2007, 2009, 2010, 2012, 2013, 2014, 2015, 2016, 2017, 2018, 2019, 2020, 2021, 2022, 2023, 2026, 2027, 2028,
2029, 2030, 2031, 2032, 2034, 2035, 2036, 2037, 2038, 2039, 2041, 2042, 2043, 2044, 2045, 2046, 2047, 2048, 2049
, 2050, 2051, 2052, 2053, 2054, 2055, 2056, 2057, 2059, 2060, 2066, 2067, 2068, 2071, 2073, 2074, 2075, 2076, 20
77, 2078, 2080]

Instantiate the MolGAN model and set the learning rate and maximum number of atoms as the size of the vertices.
Then, we create the dataset in the format of the input to MolGAN.

# create model
gan = MolGAN(learning_rate=ExponentialDecay(0.001, 0.9, 5000), vertices=num_atoms)
dataset = dc.data.NumpyDataset([x.adjacency_matrix for x in features],[x.node_features for x in features])

Define the iterbatches function because the gan_fit function requires an iterable for the batches.

def iterbatches(epochs):
for i in range(epochs):
for batch in dataset.iterbatches(batch_size=gan.batch_size, pad_batches=True):
flattened_adjacency = torch.from_numpy(batch[0]).view(-1).to(dtype=torch.int64) # flatten the input becau
invalid_mask = (flattened_adjacency < 0) | (flattened_adjacency >= gan.edges) # edge type cannot be negat
clamped_adjacency = torch.clamp(flattened_adjacency, 0, gan.edges-1) # clamp the input so it can be fed t
adjacency_tensor = one_hot(clamped_adjacency, num_classes=gan.edges) # actual one_hot
adjacency_tensor[invalid_mask] = torch.zeros(gan.edges, dtype=torch.long) # make the invalid entries, a v
adjacency_tensor = adjacency_tensor.view(*batch[0].shape, -1) # reshape to original shape and change dtyp

flattened_node = torch.from_numpy(batch[1]).view(-1).to(dtype=torch.int64)
invalid_mask = (flattened_node < 0) | (flattened_node >= gan.nodes)
clamped_node = torch.clamp(flattened_node, 0, gan.nodes-1)
node_tensor = one_hot(clamped_node, num_classes=gan.nodes)
node_tensor[invalid_mask] = torch.zeros(gan.nodes, dtype=torch.long)
node_tensor = node_tensor.view(*batch[1].shape, -1)

yield {gan.data_inputs[0]: adjacency_tensor, gan.data_inputs[1]:node_tensor}

Train the model with the fit_gan function and generate molecules with the predict_gan_generator function.

gan.fit_gan(iterbatches(25), generator_steps=0.2, checkpoint_interval=5000)

generated_data = gan.predict_gan_generator(1000)

/usr/local/lib/python3.10/dist-packages/torch/autograd/graph.py:744: UserWarning: Attempting to run cuBLAS, but

there was no current CUDA context! Attempting to set the primary context... (Triggered internally at ../aten/src
/ATen/cuda/CublasHandlePool.cpp:135.)
return Variable._execution_engine.run_backward( # Calls into the C++ engine to run the backward pass
Ending global_step 349: generator average loss -3.55075, discriminator average loss -5.23049
TIMING: model fitting took 8.770 s
Generating 1000 samples

Convert the generated graphs to RDKit molecules.

nmols = feat.defeaturize(generated_data)
print("{} molecules generated".format(len(nmols)))

[13:29:24] Explicit valence for atom # 2 O, 30, is greater than permitted

[13:29:24] Explicit valence for atom # 0 C, 26, is greater than permitted
[13:29:24] non-ring atom 0 marked aromatic
1000 molecules generated
[13:29:24] Explicit valence for atom # 1 B, 7, is greater than permitted
[13:29:24] non-ring atom 2 marked aromatic
[13:29:24] Explicit valence for atom # 1 C, 11, is greater than permitted

Remove invalid molecules from list.

nmols = list(filter(lambda x: x is not None, nmols))

Print out the number of valid molecules, but training can be unstable so some the number can vary significantly.

# currently training is unstable so 0 is a common outcome

print ("{} valid molecules".format(len(nmols)))

411 valid molecules

Remove duplicate generated molecules.

nmols_smiles = [Chem.MolToSmiles(m) for m in nmols]

nmols_smiles_unique = list(OrderedDict.fromkeys(nmols_smiles))
nmols_viz = [Chem.MolFromSmiles(x) for x in nmols_smiles_unique]
print ("{} unique valid molecules".format(len(nmols_viz)))

48 unique valid molecules

Print out up to 100 unique valid molecules.

img = Draw.MolsToGridImage(nmols_viz[0:100], molsPerRow=5, subImgSize=(250, 250), maxMols=100, legends=None, returnPN

img
This is an example of what the molecules should look like.
Introduction to GROVER
In this tutorial, we will go over what Grover is, and how to get it up and running.

GROVER, or, Graph Representation frOm selfsuperVised mEssage passing tRansformer, is a novel framework proposed
by Tencent AI Lab. GROVER utilizes self-supervised tasks in the node, edge and graph level in order to learn rich
structural and semantic information of molecules from large unlabelled molecular datasets. GROVER integrates Message
Passing Networks into a Transformer-style architecture to deliver more expressive molecular encoding.

Reference Paper: Rong, Yu, et al. "Grover: Self-supervised message passing transformer on large-scale molecular data."
Advances in Neural Information Processing Systems (2020).

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Import and Setup required modules.

We will first clone the repository onto the preferred platform, then install it as a library. We will also import deepchem
and install descriptastorus.

NOTE: The original GROVER repository does not contain a setup.py file, thus we are currently using a fork which does.

# Clone the forked repository.

%cd drive/MyDrive
!git clone https://github.com/atreyamaj/grover.git

/content/drive/MyDrive
fatal: destination path 'grover' already exists and is not an empty directory.

# Navigate to the working folder.

%cd grover

/content/drive/MyDrive/grover

# Install the forked repository.

!pip install -e ./

Obtaining file:///content/drive/MyDrive/grover
Installing collected packages: grover
Running setup.py develop for grover
Successfully installed grover-1.0.0

# Install deepchem and descriptastorus.

!pip install deepchem
!pip install git+https://github.com/bp-kelley/descriptastorus

Collecting deepchem
Downloading deepchem-2.6.1-py3-none-any.whl (608 kB)

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Requirement already satisfied: scikit-learn in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.0.2)
Requirement already satisfied: numpy>=1.21 in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.21.6)
Collecting rdkit-pypi
Downloading rdkit_pypi-2022.3.1-cp37-cp37m-manylinux_2_17_x86_64.manylinux2014_x86_64.whl (22.5 MB)
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Requirement already satisfied: scipy in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.4.1)
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Installing collected packages: rdkit-pypi, deepchem
Successfully installed deepchem-2.6.1 rdkit-pypi-2022.3.1
Collecting git+https://github.com/bp-kelley/descriptastorus
Cloning https://github.com/bp-kelley/descriptastorus to /tmp/pip-req-build-_462lldf
Running command git clone -q https://github.com/bp-kelley/descriptastorus /tmp/pip-req-build-_462lldf
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Extracting semantic motif labels

The semantic motif label is extracted by scripts/save_feature.py with feature generator fgtasklabel .

!python scripts/save_features.py --data_path exampledata/pretrain/tryout.csv \

--save_path exampledata/pretrain/tryout.npz \
--features_generator fgtasklabel \
--restart

WARNING:root:No normalization for BCUT2D_MWHI

Extracting atom/bond contextual properties (vocabulary)

The atom/bond Contextual Property (Vocabulary) is extracted by scripts/build_vocab.py .

!python scripts/build_vocab.py --data_path exampledata/pretrain/tryout.csv \

--vocab_save_folder exampledata/pretrain \
--dataset_name tryout

WARNING:root:No normalization for BCUT2D_MWHI

Splitting the data

To accelerate the data loading and reduce the memory cost in the multi-gpu pretraining scenario, the unlabelled
molecular data need to be spilt into several parts using scripts/split_data.py .

!python scripts/split_data.py --data_path exampledata/pretrain/tryout.csv \

--features_path exampledata/pretrain/tryout.npz \
--sample_per_file 100 \
--output_path exampledata/pretrain/tryout

WARNING:root:No normalization for BCUT2D_MWHI

Running Pretraining on Single GPU

!python main.py pretrain \
--data_path exampledata/pretrain/tryout \
--save_dir model/tryout \
--atom_vocab_path exampledata/pretrain/tryout_atom_vocab.pkl \
--bond_vocab_path exampledata/pretrain/tryout_bond_vocab.pkl \
--batch_size 32 \
--dropout 0.1 \
--depth 5 \
--num_attn_head 1 \
--hidden_size 100 \
--epochs 3 \
--init_lr 0.0002 \
--max_lr 0.0004 \
--final_lr 0.0001 \
--weight_decay 0.0000001 \
--activation PReLU \
--backbone gtrans \
--embedding_output_type both

WARNING:root:No normalization for BCUT2D_MWHI

Training and Finetuning

Extracting Molecular Features
Given a labelled molecular dataset, it is possible to extract the additional molecular features in order to train & finetune
the model from the existing pretrained model. The feature matrix is stored as .npz .

!python scripts/save_features.py --data_path exampledata/finetune/bbbp.csv \

--save_path exampledata/finetune/bbbp.npz \
--features_generator rdkit_2d_normalized \
--restart

WARNING:root:No normalization for BCUT2D_MWHI

!python main.py finetune --data_path exampledata/finetune/bbbp.csv \

--features_path exampledata/finetune/bbbp.npz \
--save_dir model/finetune/bbbp/ \
--checkpoint_path model/tryout/model.ep3 \
--dataset_type classification \
--split_type scaffold_balanced \
--ensemble_size 1 \
--num_folds 3 \
--no_features_scaling \
--ffn_hidden_size 200 \
--batch_size 32 \
--epochs 10 \
--init_lr 0.00015

WARNING:root:No normalization for BCUT2D_MWHI

WARNING:root:No normalization for BCUT2D_MWLOW
WARNING:root:No normalization for BCUT2D_CHGHI
WARNING:root:No normalization for BCUT2D_CHGLO
WARNING:root:No normalization for BCUT2D_LOGPHI
WARNING:root:No normalization for BCUT2D_LOGPLOW
WARNING:root:No normalization for BCUT2D_MRHI
WARNING:root:No normalization for BCUT2D_MRLOW
[WARNING] Horovod cannot be imported; multi-GPU training is unsupported
Fold 0
Loading data
Number of tasks = 1
Splitting data with seed 0
100% 2039/2039 [00:00<00:00, 3681.51it/s]
Total scaffolds = 1,025 | train scaffolds = 764 | val scaffolds = 123 | test scaffolds = 138
Label averages per scaffold, in decreasing order of scaffold frequency,capped at 10 scaffolds and 20 labels: [(a
rray([0.72992701]), array([137])), (array([1.]), array([1])), (array([0.]), array([1])), (array([1.]), array([1]
)), (array([1.]), array([1])), (array([0.]), array([1])), (array([1.]), array([1])), (array([1.]), array([2])),
(array([0.]), array([2])), (array([1.]), array([1]))]
Class sizes
p_np 0: 23.49%, 1: 76.51%
Total size = 2,039 | train size = 1,631 | val size = 203 | test size = 205
Loading model 0 from model/tryout/model.ep3
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.act_func.weight".
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Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.weight".
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Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.W_h.weight".
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Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.act_func_node.weight".
Loading pretrained parameter "grover.encoders.act_func_edge.weight".
Pretrained parameter "av_task_atom.linear.weight" cannot be found in model parameters.
Pretrained parameter "av_task_atom.linear.bias" cannot be found in model parameters.
Pretrained parameter "av_task_bond.linear.weight" cannot be found in model parameters.
Pretrained parameter "av_task_bond.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear_rev.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear_rev.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear_rev.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear_rev.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.readout.cached_zero_vector" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_atom.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_atom.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_bond.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_bond.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_atom.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_atom.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_bond.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_bond.bias" cannot be found in model parameters.
GroverFinetuneTask(
(grover): GROVEREmbedding(
(encoders): GTransEncoder(
(edge_blocks): ModuleList(
(0): MTBlock(
(heads): ModuleList(
(0): Head(
(mpn_q): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_k): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_v): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
)
)
(act_func): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
(layernorm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(W_i): Linear(in_features=165, out_features=100, bias=False)
(attn): MultiHeadedAttention(
(linear_layers): ModuleList(
(0): Linear(in_features=100, out_features=100, bias=True)
(1): Linear(in_features=100, out_features=100, bias=True)
(2): Linear(in_features=100, out_features=100, bias=True)
)
(output_linear): Linear(in_features=100, out_features=100, bias=False)
(attention): Attention()
(dropout): Dropout(p=0.1, inplace=False)
)
(W_o): Linear(in_features=100, out_features=100, bias=False)
(sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
)
(node_blocks): ModuleList(
(0): MTBlock(
(heads): ModuleList(
(0): Head(
(mpn_q): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_k): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_v): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
)
)
(act_func): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
(layernorm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(W_i): Linear(in_features=151, out_features=100, bias=False)
(attn): MultiHeadedAttention(
(linear_layers): ModuleList(
(0): Linear(in_features=100, out_features=100, bias=True)
(1): Linear(in_features=100, out_features=100, bias=True)
(2): Linear(in_features=100, out_features=100, bias=True)
)
(output_linear): Linear(in_features=100, out_features=100, bias=False)
(attention): Attention()
(dropout): Dropout(p=0.1, inplace=False)
)
(W_o): Linear(in_features=100, out_features=100, bias=False)
(sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
)
(ffn_atom_from_atom): PositionwiseFeedForward(
(W_1): Linear(in_features=251, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_atom_from_bond): PositionwiseFeedForward(
(W_1): Linear(in_features=251, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_bond_from_atom): PositionwiseFeedForward(
(W_1): Linear(in_features=265, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_bond_from_bond): PositionwiseFeedForward(
(W_1): Linear(in_features=265, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(atom_from_atom_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(atom_from_bond_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(bond_from_atom_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(bond_from_bond_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(act_func_node): PReLU(num_parameters=1)
(act_func_edge): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
)
)
(readout): Readout()
(mol_atom_from_atom_ffn): Sequential(
(0): Dropout(p=0.1, inplace=False)
(1): Linear(in_features=300, out_features=200, bias=True)
(2): PReLU(num_parameters=1)
(3): Dropout(p=0.1, inplace=False)
(4): Linear(in_features=200, out_features=1, bias=True)
)
(mol_atom_from_bond_ffn): Sequential(
(0): Dropout(p=0.1, inplace=False)
(1): Linear(in_features=300, out_features=200, bias=True)
(2): PReLU(num_parameters=1)
(3): Dropout(p=0.1, inplace=False)
(4): Linear(in_features=200, out_features=1, bias=True)
)
(sigmoid): Sigmoid()
)
Number of parameters = 889,418
Moving model to cuda
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0000 loss_train: 1.027524 loss_val: 0.494863 auc_val: 0.8744 cur_lr: 0.00059 t_time: 5.5550s v_time: 0.73
79s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0001 loss_train: 0.855072 loss_val: 0.488093 auc_val: 0.8805 cur_lr: 0.00098 t_time: 5.4703s v_time: 0.74
35s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0002 loss_train: 0.802001 loss_val: 0.488020 auc_val: 0.8953 cur_lr: 0.00073 t_time: 5.5585s v_time: 0.73
17s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0003 loss_train: 0.743282 loss_val: 0.483438 auc_val: 0.8804 cur_lr: 0.00055 t_time: 5.5933s v_time: 0.73
05s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0004 loss_train: 0.705130 loss_val: 0.473394 auc_val: 0.9043 cur_lr: 0.00041 t_time: 5.5970s v_time: 0.75
58s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0005 loss_train: 0.682583 loss_val: 0.473367 auc_val: 0.8962 cur_lr: 0.00030 t_time: 5.5740s v_time: 0.72
44s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0006 loss_train: 0.659755 loss_val: 0.477886 auc_val: 0.8939 cur_lr: 0.00023 t_time: 5.5852s v_time: 0.72
88s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0007 loss_train: 0.658016 loss_val: 0.476979 auc_val: 0.8923 cur_lr: 0.00017 t_time: 5.5050s v_time: 0.72
80s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0008 loss_train: 0.647427 loss_val: 0.470443 auc_val: 0.9020 cur_lr: 0.00013 t_time: 5.5287s v_time: 0.72
95s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0009 loss_train: 0.646125 loss_val: 0.474078 auc_val: 0.8938 cur_lr: 0.00010 t_time: 5.7616s v_time: 0.72
85s
Model 0 best validation auc = 0.904320 on epoch 4
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.act_func_node.weight".
Loading pretrained parameter "grover.encoders.act_func_edge.weight".
Loading pretrained parameter "readout.cached_zero_vector".
Loading pretrained parameter "mol_atom_from_atom_ffn.1.weight".
Loading pretrained parameter "mol_atom_from_atom_ffn.1.bias".
Loading pretrained parameter "mol_atom_from_atom_ffn.2.weight".
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Loading pretrained parameter "mol_atom_from_bond_ffn.1.weight".
Loading pretrained parameter "mol_atom_from_bond_ffn.1.bias".
Loading pretrained parameter "mol_atom_from_bond_ffn.2.weight".
Loading pretrained parameter "mol_atom_from_bond_ffn.4.weight".
Loading pretrained parameter "mol_atom_from_bond_ffn.4.bias".
Moving model to cuda
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Model 0 test auc = 0.921247
Ensemble test auc = 0.921247
Fold 1
Loading data
Number of tasks = 1
Splitting data with seed 1
100% 2039/2039 [00:00<00:00, 3551.50it/s]
Total scaffolds = 1,025 | train scaffolds = 768 | val scaffolds = 132 | test scaffolds = 125
Label averages per scaffold, in decreasing order of scaffold frequency,capped at 10 scaffolds and 20 labels: [(a
rray([0.72992701]), array([137])), (array([1.]), array([2])), (array([1.]), array([3])), (array([0.8]), array([5
])), (array([1.]), array([9])), (array([1.]), array([1])), (array([1.]), array([1])), (array([1.]), array([1])),
(array([1.]), array([1])), (array([1.]), array([1]))]
Class sizes
p_np 0: 23.49%, 1: 76.51%
Total size = 2,039 | train size = 1,631 | val size = 203 | test size = 205
Loading model 0 from model/tryout/model.ep3
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.act_func_node.weight".
Loading pretrained parameter "grover.encoders.act_func_edge.weight".
Pretrained parameter "av_task_atom.linear.weight" cannot be found in model parameters.
Pretrained parameter "av_task_atom.linear.bias" cannot be found in model parameters.
Pretrained parameter "av_task_bond.linear.weight" cannot be found in model parameters.
Pretrained parameter "av_task_bond.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear_rev.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear_rev.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear_rev.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear_rev.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.readout.cached_zero_vector" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_atom.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_atom.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_bond.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_bond.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_atom.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_atom.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_bond.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_bond.bias" cannot be found in model parameters.
GroverFinetuneTask(
(grover): GROVEREmbedding(
(encoders): GTransEncoder(
(edge_blocks): ModuleList(
(0): MTBlock(
(heads): ModuleList(
(0): Head(
(mpn_q): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_k): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_v): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
)
)
(act_func): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
(layernorm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(W_i): Linear(in_features=165, out_features=100, bias=False)
(attn): MultiHeadedAttention(
(linear_layers): ModuleList(
(0): Linear(in_features=100, out_features=100, bias=True)
(1): Linear(in_features=100, out_features=100, bias=True)
(2): Linear(in_features=100, out_features=100, bias=True)
)
(output_linear): Linear(in_features=100, out_features=100, bias=False)
(attention): Attention()
(dropout): Dropout(p=0.1, inplace=False)
)
(W_o): Linear(in_features=100, out_features=100, bias=False)
(sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
)
(node_blocks): ModuleList(
(0): MTBlock(
(heads): ModuleList(
(0): Head(
(mpn_q): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_k): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_v): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
)
)
(act_func): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
(layernorm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(W_i): Linear(in_features=151, out_features=100, bias=False)
(attn): MultiHeadedAttention(
(linear_layers): ModuleList(
(0): Linear(in_features=100, out_features=100, bias=True)
(1): Linear(in_features=100, out_features=100, bias=True)
(2): Linear(in_features=100, out_features=100, bias=True)
)
(output_linear): Linear(in_features=100, out_features=100, bias=False)
(attention): Attention()
(dropout): Dropout(p=0.1, inplace=False)
)
(W_o): Linear(in_features=100, out_features=100, bias=False)
(sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
)
(ffn_atom_from_atom): PositionwiseFeedForward(
(W_1): Linear(in_features=251, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_atom_from_bond): PositionwiseFeedForward(
(W_1): Linear(in_features=251, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_bond_from_atom): PositionwiseFeedForward(
(W_1): Linear(in_features=265, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_bond_from_bond): PositionwiseFeedForward(
(W_1): Linear(in_features=265, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(atom_from_atom_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(atom_from_bond_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(bond_from_atom_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(bond_from_bond_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(act_func_node): PReLU(num_parameters=1)
(act_func_edge): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
)
)
(readout): Readout()
(mol_atom_from_atom_ffn): Sequential(
(0): Dropout(p=0.1, inplace=False)
(1): Linear(in_features=300, out_features=200, bias=True)
(2): PReLU(num_parameters=1)
(3): Dropout(p=0.1, inplace=False)
(4): Linear(in_features=200, out_features=1, bias=True)
)
(mol_atom_from_bond_ffn): Sequential(
(0): Dropout(p=0.1, inplace=False)
(1): Linear(in_features=300, out_features=200, bias=True)
(2): PReLU(num_parameters=1)
(3): Dropout(p=0.1, inplace=False)
(4): Linear(in_features=200, out_features=1, bias=True)
)
(sigmoid): Sigmoid()
)
Number of parameters = 889,418
Moving model to cuda
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0000 loss_train: 1.016377 loss_val: 0.492704 auc_val: 0.8791 cur_lr: 0.00059 t_time: 6.3182s v_time: 0.77
94s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0001 loss_train: 0.822924 loss_val: 0.487600 auc_val: 0.8680 cur_lr: 0.00098 t_time: 5.5121s v_time: 0.79
89s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0002 loss_train: 0.752341 loss_val: 0.470391 auc_val: 0.8893 cur_lr: 0.00073 t_time: 5.5443s v_time: 0.76
47s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0003 loss_train: 0.709847 loss_val: 0.468552 auc_val: 0.8863 cur_lr: 0.00055 t_time: 5.6165s v_time: 0.81
04s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0004 loss_train: 0.682037 loss_val: 0.463301 auc_val: 0.8895 cur_lr: 0.00041 t_time: 5.5689s v_time: 0.77
95s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0005 loss_train: 0.659133 loss_val: 0.464382 auc_val: 0.8914 cur_lr: 0.00030 t_time: 5.5949s v_time: 0.80
20s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0006 loss_train: 0.630823 loss_val: 0.463676 auc_val: 0.8871 cur_lr: 0.00023 t_time: 5.5311s v_time: 0.75
48s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0007 loss_train: 0.613836 loss_val: 0.460376 auc_val: 0.8912 cur_lr: 0.00017 t_time: 5.5768s v_time: 0.75
11s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0008 loss_train: 0.604636 loss_val: 0.464385 auc_val: 0.8900 cur_lr: 0.00013 t_time: 5.5764s v_time: 0.78
48s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0009 loss_train: 0.600993 loss_val: 0.461464 auc_val: 0.8902 cur_lr: 0.00010 t_time: 5.6025s v_time: 0.77
36s
Model 0 best validation auc = 0.891352 on epoch 5
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.act_func_node.weight".
Loading pretrained parameter "grover.encoders.act_func_edge.weight".
Loading pretrained parameter "readout.cached_zero_vector".
Loading pretrained parameter "mol_atom_from_atom_ffn.1.weight".
Loading pretrained parameter "mol_atom_from_atom_ffn.1.bias".
Loading pretrained parameter "mol_atom_from_atom_ffn.2.weight".
Loading pretrained parameter "mol_atom_from_atom_ffn.4.weight".
Loading pretrained parameter "mol_atom_from_atom_ffn.4.bias".
Loading pretrained parameter "mol_atom_from_bond_ffn.1.weight".
Loading pretrained parameter "mol_atom_from_bond_ffn.1.bias".
Loading pretrained parameter "mol_atom_from_bond_ffn.2.weight".
Loading pretrained parameter "mol_atom_from_bond_ffn.4.weight".
Loading pretrained parameter "mol_atom_from_bond_ffn.4.bias".
Moving model to cuda
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Model 0 test auc = 0.920000
Ensemble test auc = 0.920000
Fold 2
Loading data
Number of tasks = 1
Splitting data with seed 2
100% 2039/2039 [00:00<00:00, 3569.05it/s]
Total scaffolds = 1,025 | train scaffolds = 766 | val scaffolds = 125 | test scaffolds = 134
Label averages per scaffold, in decreasing order of scaffold frequency,capped at 10 scaffolds and 20 labels: [(a
rray([0.72992701]), array([137])), (array([1.]), array([1])), (array([1.]), array([1])), (array([1.]), array([1]
)), (array([0.]), array([1])), (array([1.]), array([1])), (array([1.]), array([1])), (array([1.]), array([1])),
(array([0.]), array([5])), (array([1.]), array([1]))]
Class sizes
p_np 0: 23.49%, 1: 76.51%
Total size = 2,039 | train size = 1,631 | val size = 203 | test size = 205
Loading model 0 from model/tryout/model.ep3
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.1.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.linear_layers.2.bias".
Loading pretrained parameter "grover.encoders.node_blocks.0.attn.output_linear.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.W_o.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.node_blocks.0.sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_atom_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_atom.act_func.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_1.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.weight".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.W_2.bias".
Loading pretrained parameter "grover.encoders.ffn_bond_from_bond.act_func.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.atom_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_atom_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.weight".
Loading pretrained parameter "grover.encoders.bond_from_bond_sublayer.norm.bias".
Loading pretrained parameter "grover.encoders.act_func_node.weight".
Loading pretrained parameter "grover.encoders.act_func_edge.weight".
Pretrained parameter "av_task_atom.linear.weight" cannot be found in model parameters.
Pretrained parameter "av_task_atom.linear.bias" cannot be found in model parameters.
Pretrained parameter "av_task_bond.linear.weight" cannot be found in model parameters.
Pretrained parameter "av_task_bond.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear_rev.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_atom.linear_rev.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear.bias" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear_rev.weight" cannot be found in model parameters.
Pretrained parameter "bv_task_bond.linear_rev.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.readout.cached_zero_vector" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_atom.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_atom.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_bond.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_atom_from_bond.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_atom.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_atom.bias" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_bond.weight" cannot be found in model parameters.
Pretrained parameter "fg_task_all.linear_bond_from_bond.bias" cannot be found in model parameters.
GroverFinetuneTask(
(grover): GROVEREmbedding(
(encoders): GTransEncoder(
(edge_blocks): ModuleList(
(0): MTBlock(
(heads): ModuleList(
(0): Head(
(mpn_q): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_k): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_v): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
)
)
(act_func): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
(layernorm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(W_i): Linear(in_features=165, out_features=100, bias=False)
(attn): MultiHeadedAttention(
(linear_layers): ModuleList(
(0): Linear(in_features=100, out_features=100, bias=True)
(1): Linear(in_features=100, out_features=100, bias=True)
(2): Linear(in_features=100, out_features=100, bias=True)
)
(output_linear): Linear(in_features=100, out_features=100, bias=False)
(attention): Attention()
(dropout): Dropout(p=0.1, inplace=False)
)
(W_o): Linear(in_features=100, out_features=100, bias=False)
(sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
)
(node_blocks): ModuleList(
(0): MTBlock(
(heads): ModuleList(
(0): Head(
(mpn_q): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_k): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
(mpn_v): MPNEncoder(
(dropout_layer): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
(W_h): Linear(in_features=100, out_features=100, bias=False)
)
)
)
(act_func): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
(layernorm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(W_i): Linear(in_features=151, out_features=100, bias=False)
(attn): MultiHeadedAttention(
(linear_layers): ModuleList(
(0): Linear(in_features=100, out_features=100, bias=True)
(1): Linear(in_features=100, out_features=100, bias=True)
(2): Linear(in_features=100, out_features=100, bias=True)
)
(output_linear): Linear(in_features=100, out_features=100, bias=False)
(attention): Attention()
(dropout): Dropout(p=0.1, inplace=False)
)
(W_o): Linear(in_features=100, out_features=100, bias=False)
(sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
)
(ffn_atom_from_atom): PositionwiseFeedForward(
(W_1): Linear(in_features=251, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_atom_from_bond): PositionwiseFeedForward(
(W_1): Linear(in_features=251, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_bond_from_atom): PositionwiseFeedForward(
(W_1): Linear(in_features=265, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(ffn_bond_from_bond): PositionwiseFeedForward(
(W_1): Linear(in_features=265, out_features=400, bias=True)
(W_2): Linear(in_features=400, out_features=100, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
(act_func): PReLU(num_parameters=1)
)
(atom_from_atom_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(atom_from_bond_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(bond_from_atom_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(bond_from_bond_sublayer): SublayerConnection(
(norm): LayerNorm((100,), eps=1e-05, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(act_func_node): PReLU(num_parameters=1)
(act_func_edge): PReLU(num_parameters=1)
(dropout_layer): Dropout(p=0.1, inplace=False)
)
)
(readout): Readout()
(mol_atom_from_atom_ffn): Sequential(
(0): Dropout(p=0.1, inplace=False)
(1): Linear(in_features=300, out_features=200, bias=True)
(2): PReLU(num_parameters=1)
(3): Dropout(p=0.1, inplace=False)
(4): Linear(in_features=200, out_features=1, bias=True)
)
(mol_atom_from_bond_ffn): Sequential(
(0): Dropout(p=0.1, inplace=False)
(1): Linear(in_features=300, out_features=200, bias=True)
(2): PReLU(num_parameters=1)
(3): Dropout(p=0.1, inplace=False)
(4): Linear(in_features=200, out_features=1, bias=True)
)
(sigmoid): Sigmoid()
)
Number of parameters = 889,418
Moving model to cuda
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0000 loss_train: 1.000364 loss_val: 0.507716 auc_val: 0.8434 cur_lr: 0.00059 t_time: 5.7976s v_time: 0.78
02s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0001 loss_train: 0.824395 loss_val: 0.504539 auc_val: 0.8560 cur_lr: 0.00098 t_time: 5.5894s v_time: 0.77
79s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0002 loss_train: 0.735137 loss_val: 0.493423 auc_val: 0.8539 cur_lr: 0.00073 t_time: 5.5191s v_time: 0.76
10s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0003 loss_train: 0.687535 loss_val: 0.487282 auc_val: 0.8597 cur_lr: 0.00055 t_time: 5.5613s v_time: 0.75
95s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0004 loss_train: 0.681197 loss_val: 0.489330 auc_val: 0.8702 cur_lr: 0.00041 t_time: 5.5513s v_time: 0.75
01s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0005 loss_train: 0.647608 loss_val: 0.488870 auc_val: 0.8618 cur_lr: 0.00030 t_time: 5.6565s v_time: 0.77
39s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0006 loss_train: 0.638494 loss_val: 0.488281 auc_val: 0.8729 cur_lr: 0.00023 t_time: 5.5400s v_time: 0.75
84s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0007 loss_train: 0.626862 loss_val: 0.490144 auc_val: 0.8702 cur_lr: 0.00017 t_time: 5.6183s v_time: 0.78
14s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0008 loss_train: 0.619776 loss_val: 0.484179 auc_val: 0.8782 cur_lr: 0.00013 t_time: 5.9662s v_time: 0.75
96s
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 10 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller th
an what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader
running slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Epoch: 0009 loss_train: 0.613262 loss_val: 0.486484 auc_val: 0.8789 cur_lr: 0.00010 t_time: 6.3030s v_time: 0.79
31s
Model 0 best validation auc = 0.878887 on epoch 9
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_q.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_k.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.heads.0.mpn_v.W_h.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.act_func.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.layernorm.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.W_i.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.0.bias".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.weight".
Loading pretrained parameter "grover.encoders.edge_blocks.0.attn.linear_layers.1.bias".
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Moving model to cuda
/usr/local/lib/python3.7/dist-packages/torch/utils/data/dataloader.py:481: UserWarning: This DataLoader will cre
ate 4 worker processes in total. Our suggested max number of worker in current system is 2, which is smaller tha
n what this DataLoader is going to create. Please be aware that excessive worker creation might get DataLoader r
unning slow or even freeze, lower the worker number to avoid potential slowness/freeze if necessary.
cpuset_checked))
Model 0 test auc = 0.888635
Ensemble test auc = 0.888635
3-fold cross validation
Seed 0 ==> test auc = 0.921247
Seed 1 ==> test auc = 0.920000
Seed 2 ==> test auc = 0.888635
overall_scaffold_balanced_test_auc=0.909961
std=0.015088

Predicting output
Extracting molecular features
If the finetuned model uses the molecular feature as input, we need to generate the molecular feature for the target
molecules as well.

!python scripts/save_features.py --data_path exampledata/finetune/bbbp.csv \

--save_path exampledata/finetune/bbbp.npz \
--features_generator rdkit_2d_normalized \
--restart

WARNING:root:No normalization for BCUT2D_MWHI

Output
The output will be saved in a file called data_pre.csv .

Congratulations! Time to join the Community!

Star DeepChem on Github

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

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sciences. Join the conversation!
An Introduction to PROTACs
David Zhang and David Figueroa
PROTACs represent an emerging wave of new therapeutics capable of modulating proteins once thought nearly
impossible to target. By eliminating rather than merely inhibiting disease-causing proteins, PROTACs address the
limitations of existing drug modalities. As PROTACs progress through clinical trials with promising results, there is
growing anticipation surrounding their therapeutic potential.

This DeepChem tutorial serves as a starting point for exploring the world of PROTACs and the exciting field of targeted
protein degradation. The tutorial is divided into five partitions:

1. Background literature
2. Data extraction
3. Featurization
4. Model deployment
5. References

With that in mind, let's jump into how we can predict efficacy of PROTAC degraders!

1. Background literature
Traditional drug modalities, such as small-molecule drugs or monoclonal antibodies, are limited to certain modes of
action, like targeting specific receptors or blocking particular pathways. Targeted protein degradation (TPD) represents
a promising new approach to modulate proteins that have been traditionally difficult to target. TPD has given rise to
major classes of molecules that have emerged as promising therapeutic approaches against various disease contexts.

1.1 Targeted protein degradation

Targeted protein degradation represents a way of leveraging the cell's natural degradation mechanisms to target
disease causing proteins. Typically, the cell maintains protein homeostasis through clearance by proteasomes or
lysosomes. By leveraging these intrinsic cellular mechanisms, TPD methods can target a variety of proteins throughout
the cell. This has given rise to a collection of TPD methods aimed at degrading proteins that may play roles across many
disease states. One of these major class of molecules is proteolysis-targeting chimera (PROTACs).

1.2 How do PROTACs work?

PROTAC molecules are ternary structures consisting of a linker, a ligand to recruit and bind to the target protein, and a
ligand to recruit the E3 ubiquitin ligase. Before we dive into how PROTACs mediate this degradation mechanism, it is
crucial to understand the underlying biological pathway that makes this all possible.

Figure 1: Molecular structure of PROTACs molecules designed to inhibit epidermal growth factor receptor (EGFR). The
PROTAC linker connects the EGFR ligand and E3 ligase which are highlighted in yellow and gray, respectively [1].

1.1.1 Ubiquitin Proteasome System

The ubiquitin proteasome system, or UPS for short, is a crucial cellular maintenance mechanism. Ubiquitin-dependent
proteolysis is a three-step process which involves ubiquitin-activating enzymes (E1), ubiquitin-conjugate enzymes (E2),
and ubiquitin-protein ligases (E3). In general, E1 activates ubiquitin, priming it for transfer to E2 which interacts with E3
at which point E3 ligases are responsible for binding of the target protein substrate for subsequent ubiquitination by E2.
Once the protein is tagged with a polyubiquitin chain, it is recognized by the proteasome, a large protease complex that
degrades that protein into peptides.

Figure 2: The ubiquitin proteasome system is one of the cell's internal degradation mechanism crucial for targetting
dysfunctional proteins. Naturally this opens up opportunities to leverage this in a therapeutic context [2].

1.1.2 Connection to PROTACs

The realization that the UPS could be leveraged for therapeutic purposes was initially made through early studies of
viruses and plants. The underlying idea involves design of small molecules capable of recruiting the E3 ligase and
inducing degradation of a protein of interest (POI). This general idea naturally extended itself to the case of PROTACs.
Together, the POI ligand, linker, and E3 ligase ligand make up the PROTAC complex responsible for protein degradation.
Note that the presence of two ligands enables simultaneous recruitment of the E3 ligase and POI, hence its
heterobifunctionality property.

Furthermore, after the POI is degraded by the proteasome, PROTACs can disassociate and continue to induce further
degradation, enabling low concentrations to be efficacious. This catalytic mechanism of action and event-drive
pharmacology prevents PROTACs from suffering the same limitations as conventional therapeutic strategies such as
drug resistance and off-target effects.

Figure 3: The mechanism of action of PROTACs center around the UPS. In a heterobifunctional manner, recruiting both
a target protein of interest and an E3 ligase, PROTACs are able to promote protein degradation in diseases [3].

1.3 Molecular Glues

It is worth noting that PROTACs are not the only TPD method. Another major class which which also leverages the UPS to
elicit degradation are molecular glues. As implied by its name, molecular glues stabilize protein-protein interactions
between the target protein and E3 ligase. Notice how this is different than PROTACs which consists of two separate
binding ligands connected by a linker. Consequently, molecular glues may be less sterically hindered without the need
for a linker. However, identifying binding sites to induce new protein-protein interactions is typically harder than
accomodating for existing ligands, as in the case for PROTACs, making it harder to design molecular glues.
Figure 4: Lenalidomide is a molecular glue which mediates the interaction between CRBN, an E3 ligase, and CK1α,
resulting in subsequent ubiquitination. [4]

1.4 How can we leverage machine learning?

As a novel and promising technique, PROTACs have demonstrated positive clinical results thus far. However, much of
the clinical validation has been against classically drugged targets. In order for PROTACs to reach their full potential,
their clinical efficacy against novel or hard to reach targets must be demonstrated. Consequently, there has been
growing research in designing PROTAC molecules capable of elicting an effective response. However, much of the
current work is empirical and requires extensive trial-and-error processes. Machine learning could potentially
revolutionize this. By correlating molecular structure with physiochemical properties and biological activity, we could
potentially streamline the discovery process, significantly reducing the time and cost associated with validation. With
that in mind, let's jump into this tutorial to predict efficacy of PROTAC degraders!

For a more in-depth dive into PROTACs, ubiquitin proteasome system, and targeted protein degradation, readers are
referred to [5] and [6].

2. Data extraction
Before we proceed, let's install deepchem into our colab environment.

!pip install deepchem

Collecting deepchem
Downloading deepchem-2.8.0-py3-none-any.whl (1.0 MB)
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eepchem) (2.8.2)
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2023.4)
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n->deepchem) (3.5.0)
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chem) (1.3.0)
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>pandas->deepchem) (1.16.0)
Installing collected packages: rdkit, deepchem
Successfully installed deepchem-2.8.0 rdkit-2023.9.6

Now let's download this dataset on PROTACs, curated by [7], which includes 3270 PROTACs.

# Python library imports

import os

# DeepChem and scientific library imports

import deepchem as dc
import rdkit
from rdkit import Chem
from rdkit.Chem import Draw

# Third-party library imports

import pandas as pd
import numpy as np
import matplotlib.pyplot as plt

os.system('wget https://deepchemdata.s3.us-west-1.amazonaws.com/datasets/protac_10_06_24.csv')

protac_db = pd.read_csv('protac_10_06_24.csv')

Note that there exists a many-to-many mapping between PROTAC compounds and target proteins. A single PROTAC
compound can be designed to target multiple proteins, and conversely, multiple PROTAC compounds can be developed
to target the same protein. This many-to-many relationship allows for greater flexibility and adaptability in the design
and application of PROTACs.

print('''In this dataset, there are {} unique PROTAC compounds, targeting {} unique proteins for a total of {} combin
len(protac_db['Target'].unique()),
protac_db

In this dataset, there are 3270 unique PROTAC compounds, targeting 323 unique proteins for a total of 5388 combi
nations

Compound E3 DC50
Uniprot Target PDB Name Smiles
ID ligase (nM)

0 1 Q9NPI1 BRD7 VHL NaN NaN COC1=CC(C2=CN(C)C(=O)C3=CN=CC=C23)=CC(OC)=C1CN... NaN

1 1 Q9H8M2 BRD9 VHL NaN NaN COC1=CC(C2=CN(C)C(=O)C3=CN=CC=C23)=CC(OC)=C1CN... NaN

2 2 Q9NPI1 BRD7 VHL NaN NaN COC1=CC(C2=CN(C)C(=O)C3=CN=CC=C23)=CC(OC)=C1CN... NaN

3 2 Q9H8M2 BRD9 VHL NaN NaN COC1=CC(C2=CN(C)C(=O)C3=CN=CC=C23)=CC(OC)=C1CN... NaN

4 3 Q9H8M2 BRD9 CRBN NaN NaN COC1=CC(C2=CN(C)C(=O)C3=CN=CC=C23)=CC(OC)=C1CN... NaN

... ... ... ... ... ... ... ... ...

5383 3266 O60885 BRD4 FEM1B NaN NaN CC1=C(C)C2=C(S1)N1C(C)=NN=C1[C@H](CC(=O)NCCOCC... 1600

BCR-
5384 3267 NaN FEM1B NaN NaN CC1=NC(NC2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)=CC(... NaN
ABL

BCR-
5385 3268 NaN FEM1B NaN NaN CC1=NC(NC2=NC=C(C(=O)NC3=C(C)C=CC=C3Cl)S2)=CC(... NaN
ABL

ARV- O=C1CC[C@H]
5386 3269 P03372 ER CRBN NaN 2
471 (N2CC3=CC(N4CCN(CC5CCN(C6=CC=C([C@@...

ARV-
5387 3270 P10275 AR CRBN NaN N#CC1=CC=C(O[C@H]2CC[C@H](NC(=O)C3=CC=C(N4CCC(... 1
110

5388 rows × 89 columns

Taking a closer look at the dataset, each PROTAC compound has a SMILEs representation along with its target protein of
interest and E3 ligase. For reference, here is an example:

example = protac_db.iloc[0]
print('''Here is the SMILEs representation of a PROTAC compound: {}
designed to target {} protein through ubiquitination by {} E3 ligase.'''.format(example['Smiles'], example['Target'
Here is the SMILEs representation of a PROTAC compound: COC1=CC(C2=CN(C)C(=O)C3=CN=CC=C23)=CC(OC)=C1CN1CCN(CCOCC
OCC(=O)N[C@H](C(=O)N2C[C@H](O)C[C@H]2C(=O)NCC2=CC=C(C3=C(C)N=CS3)C=C2)C(C)(C)C)CC1
designed to target BRD7 protein through ubiquitination by VHL E3 ligase.

protac_db.columns

Index(['Compound ID', 'Uniprot', 'Target', 'E3 ligase', 'PDB', 'Name',

'Smiles', 'DC50 (nM)', 'Dmax (%)', 'Assay (DC50/Dmax)',
'Percent degradation (%)', 'Assay (Percent degradation)',
'IC50 (nM, Protac to Target)', 'Assay (Protac to Target, IC50)',
'EC50 (nM, Protac to Target)', 'Assay (Protac to Target, EC50)',
'Kd (nM, Protac to Target)', 'Assay (Protac to Target, Kd)',
'Ki (nM, Protac to Target)', 'Assay (Protac to Target, Ki)',
'delta G (kcal/mol, Protac to Target)',
'delta H (kcal/mol, Protac to Target)',
'-T*delta S (kcal/mol, Protac to Target)',
'Assay (Protac to Target, G/H/-TS)', 'kon (1/Ms, Protac to Target)',
'koff (1/s, Protac to Target)', 't1/2 (s, Protac to Target)',
'Assay (Protac to Target, kon/koff/t1/2)', 'IC50 (nM, Protac to E3)',
'Assay (Protac to E3, IC50)', 'EC50 (nM, Protac to E3)',
'Assay (Protac to E3, EC50)', 'Kd (nM, Protac to E3)',
'Assay (Protac to E3, Kd)', 'Ki (nM, Protac to E3)',
'Assay (Protac to E3, Ki)', 'delta G (kcal/mol, Protac to E3)',
'delta H (kcal/mol, Protac to E3)',
'-T*delta S (kcal/mol, Protac to E3)', 'Assay (Protac to E3, G/H/-TS)',
'kon (1/Ms, Protac to E3)', 'koff (1/s, Protac to E3)',
't1/2 (s, Protac to E3)', 'Assay (Protac to E3, kon/koff/t1/2)',
'IC50 (nM, Ternary complex)', 'Assay (Ternary complex, IC50)',
'EC50 (nM, Ternary complex)', 'Assay (Ternary complex, EC50)',
'Kd (nM, Ternary complex)', 'Assay (Ternary complex, Kd)',
'Ki (nM, Ternary complex)', 'Assay (Ternary complex, Ki)',
'delta G (kcal/mol, Ternary complex)',
'delta H (kcal/mol, Ternary complex)',
'-T*delta S (kcal/mol, Ternary complex)',
'Assay (Ternary complex, G/H/-TS)', 'kon (1/Ms, Ternary complex)',
'koff (1/s, Ternary complex)', 't1/2 (s, Ternary complex)',
'Assay (Ternary complex, kon/koff/t1/2)',
'IC50 (nM, Cellular activities)', 'Assay (Cellular activities, IC50)',
'EC50 (nM, Cellular activities)', 'Assay (Cellular activities, EC50)',
'GI50 (nM, Cellular activities)', 'Assay (Cellular activities, GI50)',
'ED50 (nM, Cellular activities)', 'Assay (Cellular activities, ED50)',
'GR50 (nM, Cellular activities)', 'Assay (Cellular activities, GR50)',
'PAMPA Papp (nm/s, Permeability)', 'Assay (Permeability, PAMPA Papp)',
'Caco-2 A2B Papp (nm/s, Permeability)',
'Assay (Permeability, Caco-2 A2B Papp)',
'Caco-2 B2A Papp (nm/s, Permeability)',
'Assay (Permeability, Caco-2 B2A Papp)', 'Article DOI',
'Molecular Weight', 'Exact Mass', 'XLogP3', 'Heavy Atom Count',
'Ring Count', 'Hydrogen Bond Acceptor Count',
'Hydrogen Bond Donor Count', 'Rotatable Bond Count',
'Topological Polar Surface Area', 'Molecular Formula', 'InChI',
'InChI Key'],
dtype='object')

In general, the PROTAC-DB dataset contains information for a variety of different physiochemical and biochemical
properties of PROTAC structures. Several useful ones to point out are

, which describes the spontaneity of a chemical reaction,

which measures the concentration of a ligand to achieve 50% occupancy of the protein binding sites, and

which measures a compound's solubility, an indication of its absorption and distribution characteristics.

Before we proceed, let's plot the distribution of each of these properties to get a better sense of our PROTAC dataset
starting with ΔG values.

delta_G = protac_db['delta G (kcal/mol, Protac to E3)']

delta_G = delta_G.dropna()
delta_G = delta_G.astype(float)
plt.hist(delta_G, bins=10)
plt.xlabel('ΔG (kcal/mol)')
plt.ylabel('Frequency')
plt.title(f'Distribution of ΔG across PROTAC molecules')
plt.plot()

[]
Let's take a closer look at the distribution of PROTAC molecules around the -10 range of ΔG values.

delta_G = protac_db['delta G (kcal/mol, Protac to E3)']

delta_G = delta_G.dropna()
delta_G = delta_G.astype(float)

x_min = -15
x_max = -5
bin_size = 1
bins = np.arange(x_min, x_max, bin_size)

plt.hist(delta_G, bins=bins)
plt.xlabel('ΔG (kcal/mol)')
plt.ylabel('Frequency')
plt.title('Distribution of ΔG ranged from -15 to -5 across PROTAC molecules')
plt.plot()

[]

There does not appear to be a lot of information on the spontaneity of PROTAC reactions but it is worth noting that the
ones with recorded ΔGs appear energetically favorable, as expected.
Let's now take a look at the

values.

kd_data = protac_db['Kd (nM, Ternary complex)']

kd_data = kd_data.dropna()
kd_data = kd_data[~kd_data.str.contains('/')]
kd_data = kd_data.astype(float)
plt.hist(kd_data)
plt.xlabel('Dissociation constant (nM)')
plt.ylabel('Frequency')
plt.title('Distribution of Kd values across PROTAC molecules')
plt.plot()

[]

Similar to ΔG values, there does not appear to be a lot of information on the affinity of formed PROTAC complexes. Since
the range is so large, let's plot a second histogram focused on the PROTACs with low

kd_data = protac_db['Kd (nM, Ternary complex)']

kd_data = kd_data.dropna()
kd_data = kd_data[~kd_data.str.contains('/')]
kd_data = kd_data.astype(float)

# limit range
x_max = 1500
x_min = 0
bin_size = 25
bins = np.arange(x_min, x_max, bin_size)

plt.hist(kd_data, bins=bins)

plt.xlabel('Dissociation constant (nM)')

plt.ylabel('Frequency')
plt.title('Distribution of Kd values ranged from 0-1500 across PROTAC molecules')
plt.plot()

[]
The improved resolution of values illustrates a much cleaner distribution of

values. We do see that a number of them have low, favorable

values indicating that the PROTAC linker can form a strong connection with the E3 ligase and target protein.

Let's now take a look at XLogP3 values. Note that this is slightly different than the typical LogP partition coefficient.
Recall that LogP is defined

In other words, LogP is the measured ratio of the concentration of a compound in the organic phase to the its
concentration in the aqueous phase, measuring the compound's solubility. XLogP3 is a knowledge-based method for
calculating the partition coefficient by accounting for the molecular structure, presence of functional groups, and
bonding [8]. Both properties estimate a compound's liphophilicity, giving insight into how a compound may behave in
biological systems.

plt.hist(protac_db['XLogP3'])
plt.xlabel('XLogP3 Values')
plt.ylabel('Frequency')
plt.title('Distribution of XLogP3 values across PROTAC molecules')
plt.plot()

[]
All PROTAC compounds have a recorded XLogP3 value. The distribution looks normally distributed with few molecules
with extreme logP profiles.

Now, let's take a look at the PROTAC degradation properties. "DC50 (nM)" and "Dmax (%)" represent the half maximal
degradation concentration and maximal degradation of the target protein of interest, respectively. Let's take a quick
look at their distributions.

Let's first do some data cleaning

# Let's first drop all the NaN values

raw_dc50 = protac_db['DC50 (nM)']
raw_dc50 = raw_dc50.dropna()

Notice that the values are all in string format with non-numerical characters such as '<', '/', and '>'. For the time being,
let's remove these values.

raw_dc50 = raw_dc50[~raw_dc50.str.contains('<|>|/|~|-')]
raw_dc50 = raw_dc50.astype(float)

plt.hist(raw_dc50.values, bins=75)
plt.xlabel('PROTACs')
plt.ylabel('DC50 (nM)')
plt.title('DC50 for all PROTACs')
plt.plot()

[]
The distribution is certainly skewed and has a few outliers. Let's log normalize.

lognorm_dc50 = np.log(raw_dc50)

plt.hist(lognorm_dc50, bins=15)
plt.xlabel('Log normalized DC50 values (log nM)')
plt.ylabel('Frequency')
plt.title('Distribution of log normalized DC50 values')
plt.plot()

[]

Now, let's take a look at Dmax percentage which represents the maximal degradation a PROTAC can elicit relative to
the total activity of the target protein of interest [7].
# Using the same row indices as our cleaned DC50 data
dmax = protac_db.iloc[lognorm_dc50.index]['Dmax (%)']

# Following the same data cleaning procedure:

dmax = dmax.dropna()
dmax = dmax[~dmax.str.contains('<|>|/|~|-')]
dmax = dmax.astype(float)

plt.hist(dmax.values, bins=10)
plt.xlabel('Dmax (%)')
plt.ylabel('Frequency')
plt.title('Distribution of Dmax (%)')
plt.plot()

[]

Notice that Dmax is represented as a percentage. For now, let's continue with regressing on DC50. We are now ready to
featurize!

# Let's predict DC50 properties for the time being

cleaned_data = protac_db.iloc[lognorm_dc50.index]
print('There are {} PROTAC samples.'.format(cleaned_data.shape[0]))

There are 599 PROTAC samples.

protac_smiles = cleaned_data['Smiles']
dc_vals = lognorm_dc50

3. Featurization
Let's featurize using CircularFingerprint which is incorporated in DeepChem! CircularFingerprint is a common featurizer
for molecules that encode local information about each atom and their neighborhood. For more information, the reader
is refered to [9].

from rdkit import Chem

featurizer = dc.feat.CircularFingerprint(radius=4, chiral=True)

features = featurizer.featurize(protac_smiles)

# Let's initialize our dataset and perform splits

dataset = dc.data.NumpyDataset(X = features, y = dc_vals, ids=list(protac_smiles))

splitter = dc.splits.RandomSplitter()
train_random, val_random, test_random = splitter.train_valid_test_split(dataset, seed=42)

Along with a random split, let's also use a scaffold split which ensures that the split contain a structurally diverse array
of compounds. Scaffold split groups molecules according to presence of rings, linkers, combinations of rings and linkers,
as well as atomic properties. In general, scaffold splits are a good way of ensuring generalizability of our models.
# Scaffold split
splitter = dc.splits.ScaffoldSplitter()
train_scaffold, val_scaffold, test_scaffold = splitter.train_valid_test_split(dataset, seed=42)

To see the scaffold split in action, let's visualize the chosen compounds across the splits.

print("Three molecules from the train set:")

np.random.seed(42)
indices = np.random.choice(len(train_scaffold), size=3, replace=False)

smiles = [train_scaffold.ids[index] for index in indices]

mols = [Chem.MolFromSmiles(smile) for smile in smiles]

Draw.MolsToGridImage(mols, molsPerRow=3, subImgSize=(450, 350))

Three molecules from the train set:

print("Three molecules from the validation set:")

indices = np.random.choice(len(val_scaffold), size=3, replace=False)

smiles = [val_scaffold.ids[index] for index in indices]

mols = [Chem.MolFromSmiles(smile) for smile in smiles]

Draw.MolsToGridImage(mols, molsPerRow=3, subImgSize=(450, 350))

Three molecules from the validation set:

print("Five molecules from the test set:")

indices = np.random.choice(len(test_scaffold), size=3, replace=False)

smiles = [test_scaffold.ids[index] for index in indices]

mols = [Chem.MolFromSmiles(smile) for smile in smiles]

Draw.MolsToGridImage(mols, molsPerRow=3, subImgSize=(450, 350))

Five molecules from the test set:

There are certainly functional group differences spread throughout the splits. Notice the presence of the nitrile group in
the train set, amine group in the validation set, as well as the sulfonamide group in the test set.

Additionally, notice the structural and conformational differences among the various data splits. It will be interesting to
see how well our model generalizes.
4. Model deployment
We have successfully generated our train and test datasets. Let's now create a simple MLP model to predict PROTAC
degradation properties!

# Initialize a 2 layer FCN

import torch
import torch.nn as nn

n_tasks = 1
n_features = train_random.X.shape[1]
layer_sizes = [256, 32, 1]
dropouts = [0.0, 0.2, 0]
activation_fns = [nn.ReLU(), nn.ReLU(), nn.Identity()]

optimizer = dc.models.optimizers.Adam()

# Let's log every train epoch

batch_size = 10
log_freq = int(len(train_random) / batch_size +1)

# L2 loss is default
protac_model_random = dc.models.MultitaskRegressor(n_tasks, n_features, layer_sizes, dropouts=dropouts, activation_fn
optimizer=optimizer, batch_size=10, log_frequency=log_freq)
protac_model_scaffold = dc.models.MultitaskRegressor(n_tasks, n_features, layer_sizes, dropouts=dropouts, activation_
optimizer=optimizer, batch_size=10, log_frequency=log_freq)

Let's now wrap everything together to instantiate a DeepChem model! Note that due to the small sample size, a smaller
batch size actually helps performance.

# protac_model = dc.models.torch_models.TorchModel(protac_model, loss=criterion, optimizer=optimizer, batch_size=10,

param_count = sum(p.numel() for p in protac_model_random.model.parameters() if p.requires_grad)
print("There are {} trainable parameters".format(param_count))
protac_model_random.model

There are 532805 trainable parameters

PytorchImpl(
(layers): ModuleList(
(0): Linear(in_features=2048, out_features=256, bias=True)
(1): Linear(in_features=256, out_features=32, bias=True)
(2): Linear(in_features=32, out_features=1, bias=True)
)
(output_layer): Linear(in_features=1, out_features=1, bias=True)
(uncertainty_layer): Linear(in_features=1, out_features=1, bias=True)
)

Let's define the validation function to prevent overfitting.

train_losses_random = []
val_losses_random = []

train_losses_scaffold = []
val_losses_scaffold = []

metric = [dc.metrics.Metric(dc.metrics.mean_squared_error)]

n_epochs=100
for i in range(n_epochs):
protac_model_random.fit(train_random, nb_epoch=1, all_losses=train_losses_random)

protac_model_scaffold.fit(train_scaffold, nb_epoch=1, all_losses=train_losses_scaffold)

# Validate on every other epoch

if i % 2 == 0:
loss = protac_model_random.evaluate(val_random, metrics=metric)
val_losses_random.append(loss['mean_squared_error'])

loss = protac_model_scaffold.evaluate(val_scaffold, metrics=metric)

val_losses_scaffold.append(loss['mean_squared_error'])

We can easily look at how the training went through plotting the recorded losses.

train_steps = [(i+1)*log_freq for i in range(len(train_losses_random))]

val_steps = [(i+1)*(log_freq*2) for i in range(len(val_losses_random))]

fig, ax = plt.subplots(1, 2, figsize=(12, 5))

ax[0].plot(train_steps, train_losses_random, label='Train loss')

ax[0].plot(val_steps, val_losses_random, label='Val loss')
ax[0].legend()
ax[0].set_xlabel('Frequency of Steps')
ax[0].set_ylabel('Loss')
ax[0].set_title('Loss across train and validation random split')

ax[1].plot(train_steps, train_losses_scaffold, label='Train loss')

ax[1].plot(val_steps, val_losses_scaffold, label='Val loss')
ax[1].legend()
ax[1].set_xlabel('Frequency of Steps')
ax[1].set_ylabel('Loss')
ax[1].set_title('Loss across train and validation scaffold split')

plt.plot()

[]

We can see that the model performs less well on the scaffold validation set which makes sense as the scaffold splits
ensures that more validation molecules are out of distribution relative to the train distribution.

Let's now perform some inference on our test set to evaluate our models!

metrics = [dc.metrics.Metric(dc.metrics.mean_squared_error), dc.metrics.Metric(dc.metrics.pearsonr), dc.metrics.Metri

eval_metrics = protac_model_random.evaluate(test_random, metrics)
preds = protac_model_random.predict(test_random)

for k, v in eval_metrics.items():
print('{}: {}'.format(k, v))

mean_squared_error: 3.074001339280645
pearsonr: 0.818568671566446
pearson_r2_score: 0.6700546700700561

import seaborn as sns

preds_and_labels = np.concatenate((test_random.y.reshape([60, 1]), preds.reshape([60, 1])), axis=1)
pred_df = pd.DataFrame(preds_and_labels, columns=['Actual log DC50 values', 'Predicted log DC50 values'])
sns.jointplot(pred_df, x='Predicted log DC50 values', y='Actual log DC50 values')
plt.annotate(f"R: {eval_metrics['pearsonr']:.2f}\nR²: {eval_metrics['pearson_r2_score']:.2f}",
xy=(0.05, 0.95),
xycoords='axes fraction',
ha='left',
va='top',
fontsize=12,
bbox=dict(boxstyle='round,pad=0.5', edgecolor='black', facecolor='white'))
# Set the title
plt.suptitle('Predicted vs Actual log DC50 Values from Random Split')

# Adjust the position of the title to avoid overlap with the plot
plt.tight_layout()
plt.show()
The random split appears to do fairly well. Let's see how well our model does on the scaffold split.

metrics = [dc.metrics.Metric(dc.metrics.mean_squared_error), dc.metrics.Metric(dc.metrics.pearsonr), dc.metrics.Metri

eval_metrics = protac_model_scaffold.evaluate(test_scaffold, metrics)
preds = protac_model_scaffold.predict(test_scaffold)

for k, v in eval_metrics.items():
print('{}: {}'.format(k, v))

mean_squared_error: 5.991774828135091
pearsonr: -0.10286796793151554
pearson_r2_score: 0.010581818826359309

import seaborn as sns

preds_and_labels = np.concatenate((test_scaffold.y.reshape([60, 1]), preds.reshape([60, 1])), axis=1)
pred_df = pd.DataFrame(preds_and_labels, columns=['Actual log DC50 values', 'Predicted log DC50 values'])
sns.jointplot(pred_df, x='Predicted log DC50 values', y='Actual log DC50 values')
plt.annotate(f"R: {eval_metrics['pearsonr']:.2f}\nR²: {eval_metrics['pearson_r2_score']:.2f}",
xy=(0.05, 0.95),
xycoords='axes fraction',
ha='left',
va='top',
fontsize=12,
bbox=dict(boxstyle='round,pad=0.5', edgecolor='black', facecolor='white'))
# Set the title
plt.suptitle('Predicted vs Actual log DC50 Values from Scaffold Split')

# Adjust the position of the title to avoid overlap with the plot
plt.tight_layout()
plt.show()
The model does significantly worse on the held out scaffold test set which was expected given the simplicity of the
model. Developing far more complex models which can generalize out of distribution is a key area of focus in many
areas of research from molecule property prediction to computer vision to natural language processing. In general, I
hope this tutorial was a informative introduction into the world of PROTACs. Follow along as we explore how we can
think about PROTAC design in the next tutorial!

5. References
[1] Kelm, J.M., Pandey, D.S., Malin, E. et al. PROTAC’ing oncoproteins: targeted protein degradation for cancer therapy.
Mol Cancer. 2023, 22, 62. https://doi.org/10.1186/s12943-022-01707-5

[2] Tu, Y., Chen, C., Pan, J., Xu, J., Zhou, Z. G., & Wang, C. Y. The Ubiquitin Proteasome Pathway (UPP) in the regulation
of cell cycle control and DNA damage repair and its implication in tumorigenesis. International journal of clinical and
experimental pathology. 2012, 5, 8.

[3] Sun, X., Gao, H., Yang, Y. et al. PROTACs: great opportunities for academia and industry. Sig Transduct Target Ther.
2019, 4, 64. https://doi.org/10.1038/s41392-019-0101-6

[4] Che Y, Gilbert AM, Shanmugasundaram V, Noe MC. Inducing protein-protein interactions with molecular glues. Bioorg
Med Chem Lett. 2018, 28, 15. https://doi.org/10.1016/j.bmcl.2018.04.046.

[5] Békés, M., Langley, D.R. & Crews, C.M. PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug
Discov. 2022, 21, 181–200. https://doi.org/10.1038/s41573-021-00371-6

[6] Liu, Z., Hu, M., Yang, Y. et al. An overview of PROTACs: a promising drug discovery paradigm. Mol Biomed. 2022, 3
(46). https://doi.org/10.1186/s43556-022-00112-0

[7] Gaoqi Weng, Xuanyan Cai, Dongsheng Cao, Hongyan Du, Chao Shen, Yafeng Deng, Qiaojun He, Bo Yang, Dan Li,
Tingjun Hou, PROTAC-DB 2.0: an updated database of PROTACs, Nucleic Acids Research. 2023, 51 (D1), Pages D1367–
D1372, https://doi.org/10.1093/nar/gkac946

[8] Cheng T, Zhao Y, Li X, Lin F, Xu Y, Zhang X, Li Y, Wang R, Lai L. Computation of octanol-water partition coefficients
by guiding an additive model with knowledge. J Chem Inf Model. 2007, 47 (6), 2140-8.
https://doi.org/10.1021/ci700257y.

[9] Glem RC, Bender A, Arnby CH, Carlsson L, Boyer S, Smith J. Circular fingerprints: flexible molecular descriptors with
applications from physical chemistry to ADME. IDrugs. 2006, 9 (3).
Congratulations! Time to join the Community!
Congratulations on completing this tutorial notebook! If you enjoyed working through the tutorial, and want to continue
working with DeepChem, we encourage you to finish the rest of the tutorials in this series. You can also help the
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Druggability Assessment with Fpocket and Machine
Learning
Author: Anamika Yadav

Table of Contents:
Introduction
Understanding Druggability
Methods to assess drugabililty
Application of Machine Learning in Druggability Assessment
Practical Application of Machine Learning for Druggability Prediction
Building a dataset
Fpocket to idneitfy binding pockets
ML model to classify the binding pockets

Introduction
In this tutorial, we will explore the concept of druggability and its crucial role in identifying successful drug targets. We
will then apply a machine learning model to classify drug targets as highly druggable or less druggable, helping us
assess the potential of a protein to be effectively targeted by a drug.

Understanding Druggability
Protein Pockets

Protein pockets, also known as binding pockets or active sites, are regions on the surface of a protein where small
molecules, such as drugs, can bind. These pockets are formed by the three-dimensional folding of the protein. Protein
pockets are characterized by specific amino acids lining the pocket that interact with ligands through various forces,
such as hydrogen bonds, hydrophobic interactions, van der Waals forces, and ionic bonds. These pockets are crucial as
they can be active sites where catalytic activity occurs, or allosteric sites where binding modulates the protein's function
without directly involving the active site.

Identifying protein pockets or binding sites on disease-related proteins is essential for selecting targets for new drugs.
Once a binding site is known, drugs can be designed to fit precisely into these sites, enhancing their efficacy and
reducing side effects. Understanding the binding site helps in modifying drug molecules to increase their affinity and
specificity.

Binding sites are central to the concept of druggability, as they are the points of interaction between a drug and its
target protein. The characteristics of binding sites, such as their geometric and chemical properties, determine whether
a protein can be effectively targeted by a drug. By understanding and analyzing these sites, we can identify druggable
targets, design and optimize drugs, and predict the druggability of new proteins, ultimately facilitating the development
of effective and safe therapeutic agents.

To learn more about binding sites, check out this additional DeepChem tutorial on the topic: Introduction to Binding
Sites

Druggability

Druggability is the measure of whether a biological drug target, like a protein, can be effectively targeted and
modulated by a drug to treat a disease. It basically refers to how suitable a protein is for being targeted by a drug. Not
all proteins are good drug targets. A druggable protein has certain characteristics that make it possible to design a drug
to interact with it effectively. For instance, a druggable protein must have accessible and well-defined binding sites or
pockets that can interact with drug molecules.
Fig. 1: Druggable pocket correspond to a protein region capable of binding a drug-like molecule.(source)

Properties of a Druggable Target

Structurally, a druggable target must have well-defined binding pockets where potential drugs can bind. These pockets,
identified through techniques like X-ray crystallography or computational modeling, should be of suitable size, shape,
and chemical composition to accommodate drug-like molecules.

The identification and characterization of binding pockets involve a detailed analysis of their key properties, including
volume, hydrophobicity, and the presence of polar residues. The volume of a binding pocket dictates the size of the
ligands that can be accommodated, with larger pockets able to bind larger or more complex molecules, offering more
points of interaction. However, excessively large pockets can sometimes be less selective, leading to off-target effects.
Hydrophobic regions within the binding pocket interact with non-polar parts of drug molecules through van der Waals
forces and hydrophobic interactions, crucial for the binding stability of many drugs, particularly those targeting
intracellular proteins where the environment is less aqueous. Polar residues within the pocket can form hydrogen bonds
and ionic interactions with the drug, which are often key determinants of binding affinity and specificity. The distribution
and accessibility of these polar residues are carefully analyzed to optimize drug design.

Another critical aspect of binding pockets is their dynamic behavior and flexibility. Binding pockets are not always static;
they can undergo conformational changes upon ligand binding. This dynamic behavior, known as induced fit, allows the
pocket to better accommodate different ligands, enhancing binding affinity and specificity. Molecular dynamics
simulations are particularly useful in studying these conformational changes, providing insights into how flexible pockets
can adapt to various drug molecules. Understanding this flexibility is essential for designing drugs that can bind
effectively even as the protein changes shape.

The balance between hydrophobic and hydrophilic areas within the pocket also influences the type of ligands that can
bind effectively. Hydrophobic pockets are better suited for non-polar ligands, while hydrophilic or polar pockets favor
ligands that can form hydrogen bonds and ionic interactions. The density and distribution of alpha spheres, geometric
constructs used to model the cavities within binding pockets, help in understanding the compactness and accessibility
of the pocket. A high alpha sphere density typically indicates a well-defined pocket with the potential for strong ligand
interactions. Additionally, the surface area of the pocket, particularly the solvent-accessible surface area (SASA), is
crucial as it indicates how much of the pocket is exposed and available for binding, providing further insights into the
druggability of the target.

Why is Druggability Important?

Before investing a lot of time and money into developing a new drug, scientists want to ensure that the target they are
aiming at has a good chance of responding to a drug. If a target is druggable, it means there's a better chance that a
drug can bind to it, affect its function, and ultimately help treat the disease. This helps prioritize targets that are more
likely to lead to successful drug development.

Despite decades of experimental investigations in the drug discovery domain, about 96% overall failure rate has been
recorded in drug development due to the “undruggability” of various identified disease targets and other challenges.
Druggability assessment of a target protein is crucial for several reasons:

1. Prioritizing "Druggable" Pockets: Not all regions of a promising target protein are suitable for drug binding.
Druggability assessment tools, such as fpocket or SiteMap, are employed to identify pockets on the protein surface
that are amenable to drug interaction. These pockets should be accessible, possess favorable physicochemical
properties (such as hydrophobicity and the presence of hydrogen bond donors/acceptors), and ideally, should not be
essential for the protein's normal function to avoid potential side effects if the pocket is targeted by a drug.

2. Reducing Risks of Off-Target Effects: Off-target effects occur when a drug interacts with unintended proteins,
leading to adverse side effects. By conducting a thorough druggability assessment, researchers can identify target
proteins with minimal risk of such interactions. This involves analyzing the protein’s structure and sequence to
detect potential promiscuous binding sites that might interact with a broad range of molecules, thereby increasing
the risk of off-target effects.

3. Predicting Potential Safety Issues: Druggability assessment can also highlight potential safety concerns related
to targeting specific proteins. For instance, if the target protein shares significant structural or sequence similarity
with proteins involved in critical biological processes, inhibiting it could lead to unintended consequences. This
consideration is essential to avoid disrupting essential functions that could lead to toxicity or other adverse effects .

Methods for Druggability Assessment

Experimental druggability assessments often utilize high-throughput or NMR-based screening with libraries of molecules
that exhibit lead-like characteristics. However, the high cost of equipment and the potential for ambiguous results, often
due to insufficient compound libraries, limit the effectiveness of these experimental approaches. As a result,
computational methods have gained prominence in recent decades, particularly those based on virtual screening and
machine learning. These approaches typically involve four primary druggability assessment methods:

1. Sequence-Based Druggability Assessment:

Sequence-based methods analyze the amino acid sequence of a protein to predict its potential as a drug target. The
sequence of amino acids determines the protein's function and can reveal conserved regions that may form binding
pockets for drugs. This method also provides insights into essential physicochemical properties such as solvent
accessibility, hydrophobicity, charge, and polarity.

Sequence-based assessments are often used in machine-learning algorithms to predict druggability. They can help
identify functional domains within a protein. However, relying solely on sequence data can be limiting, as it does not
provide a full picture of the protein's structure or how accessible these domains are to drug molecules.

Examples include CHEMBL, LncRNA2Target, and MiRBase, which are databases and tools that aid in predicting
druggability based on protein sequences.

2. Structure-Based Druggability Assessment:

Structure-based methods examine the 3D structure of a protein to identify and evaluate potential drug-binding pockets.
For a small drug-like molecule to effectively bind, the protein must have a pocket that is appropriately sized, with a
deep hydrophobic cavity to encapsulate the drug. Large, exposed polar sites are generally less druggable compared to
smaller, more hydrophobic pockets.

This method provides a more detailed and reliable prediction compared to sequence-based methods, as it considers the
physical characteristics of the protein's binding sites. The identified pockets are then compared against a reference set
of known biological targets to assess their druggability.

Notable tools include DOGSiteScorer, Metapocket, Fpocket, PockDrug Server, SiteMap, and Open Targets, which help
identify and analyze potential drug-binding pockets.

3. Ligand-Based Druggability Assessment:

Ligand-based methods focus on the likelihood that a protein can bind to known drug-like molecules, called ligands. By
examining endogenous compounds and their interactions with the target, researchers can predict how well a new drug
might interact with the protein.

This approach leverages existing data on ligands and their binding capabilities, which can provide valuable insights
when predicting the druggability of new targets.

Examples include BindingDB, PubChem, SwissTargetPrediction and TargetHunter, which are comprehensive databases
of ligand-protein interactions.

4. Precedence-Based Druggability Assessment:

This method relies on historical data of proteins that have already been successfully targeted by drugs. If a similar
protein has proven to be druggable in the past, it is more likely that a new, related target will also be druggable.

Precedence-based methods offer the highest confidence in druggability predictions because they are based on proven,
established targets. However, while this method provides a strong basis for predicting success, it does not guarantee
that new drugs targeting similar proteins will succeed.

Databases such as DrugBank, ClinicalTrials.gov, and DrugCentral store detailed information on existing drug targets and
compounds currently undergoing clinical trials.

Application of Machine Learning in Druggability Assessment

Machine-learning (ML) based methodologies can handle vast datasets, extract complex patterns, provide more accurate
predictions, and reduce human bias, ultimately speeding up the druggability assessment. Various machine learning
algorithms have been employed to develop in silico models for the druggability assessment which help to analyse
biological data, predict binding site interactions, and identify potential drug target and drug candidates.

The ML methods are categorized into supervised and unsupervised learning techniques, each serving different purposes
within the drug discovery pipeline.

The supervised learning focuses on tasks where the outcome is known and involves models like decision trees,
random forests, SVM, and Bayesian networks for tasks ranging from disease-druggability predictions to target
identification.

Unsupervised Learning involves clustering techniques like K-Means, hierarchical clustering, and HMM for tasks like
molecular designing and feature selection.

Fig 2 : Methods to predict the druggability based on machine learning (Source)

Note: For information on various ML models, please refer to the ML resources provided at the end of this tutorial. In this
section, we will concentrate on the application of ML approaches specifically in druggability assessment.

Fig 2 illustrates how various AI and machine learning (ML) techniques are applied in the assessment of druggability.

In Supervised Learning, models like Decision Trees and Random Forest are used to predict the druggability of a target,
such as a protein involved in a disease. These models can also predict the disease-drug response, which helps
determine how well a drug might work in treating a specific disease. Classification methods, like Nearest Neighbour and
SVM (Support Vector Machine), are used for drug target association, identifying which drugs are likely to interact with
which targets. NLP (Natural Language Processing) helps analyze vast amounts of scientific literature to uncover
potential drug targets, while Bayesian Networks assist in target identification, pinpointing which proteins or molecules
are the best candidates for drug development.

Unsupervised Learning focuses on Clustering techniques, such as K-Means and Hierarchical Clustering, which group
similar molecules or biological data together. This is crucial for molecular designing, where scientists design new drugs
based on the properties of these clusters. Hidden Markov Models (HMM) are used for feature selection, identifying the
most important characteristics of a protein that determine its druggability.

Application ML and AI based approaches in different Druggability Assessment methods:

1. Sequence-Based Druggability Assessment:

Supervised Learning: Nearest Neighbour, SVM, and Random Forest can be used to predict the druggability of a
target based on its sequence features (like amino acid composition and conserved regions). NLP techniques can
process and extract relevant information from genetic databases or literature to predict potential binding sites
based on sequence data.
Unsupervised Learning : Hierarchical Clustering and K-Means can group protein sequences into clusters based on
their similarities, which helps in identifying conserved regions or sequence motifs linked to druggability.

2. Structure-Based Druggability Assessment:

Supervised Learning: Decision Trees and Bayesian Networks can predict whether specific structural features (like
the size and hydrophobicity of binding pockets) make a protein druggable. Random Forest models can aggregate
predictions about various structural features to give a more accurate overall assessment.
Unsupervised Learning: Hidden Markov Models (HMMs) can model protein structural dynamics and predict how likely
a given binding site is to interact with a drug. K-Means clustering can identify common structural features across
different proteins that correlate with druggability.

3. Ligand-Based Druggability Assessment:

Supervised Learning: SVM and NLP can be used to predict drug-target associations by analyzing known ligands and
their binding affinities with various proteins. Random Forest models can improve the accuracy of these predictions
by considering multiple ligand features simultaneously.
Unsupervised Learning: K-Means and Hierarchical Clustering can group ligands based on their chemical properties,
aiding in the identification of new ligand-based druggable targets.

4. Precedence-Based Druggability Assessment:

Supervised Learning: Bayesian Networks and Decision Trees can help in predicting the success of new targets by
analyzing previous data on established drug targets and their associated compounds. Random Forests can combine
different data points from established targets to predict the druggability of new, similar targets.
Unsupervised Learning: HMMs can be used to model the progression of drug development for targets with existing
precedents, helping in feature selection and identifying key characteristics of successful targets.

Practical Application of Machine Learning for Druggability

Prediction
With a solid understanding of druggability and the application of machine learning (ML) in druggability assessment, we
are now ready to conduct an experiment to classify protein targets into 'highly druggable' and 'less druggable'
categories using a Random Forest model.

Our dataset consists of proteins paired with their corresponding druggability labels - 'highly druggable' and 'less
druggable'. To identify the druggable pockets within these proteins, we’ll utilize Fpocket, a structure-based druggability
assessment tool. Fpocket excels at identifying and characterizing pockets on the surface of proteins, which are potential
binding sites for small molecules. These pockets are key regions where drug molecules might interact with the protein
to exert a therapeutic effect.

The experiment involves two primary steps:

1. Identifying Druggable Pockets: Using Fpocket, we will analyze the protein structures to find pockets that might
serve as effective binding sites for small molecules. Fpocket evaluates various characteristics of these pockets, such
as size, shape, depth, and hydrophobicity, which are crucial indicators of druggability.

2. Training the Random Forest Model: Once we have characterized the pockets, the Random Forest model will be
trained on these features along with the corresponding druggability labels. Random Forest is a machine learning
algorithm that uses multiple learning algorithms to obtain better predictive performance than could be obtained
from any of the constituent learning algorithms alone. It operates by constructing a multitude of decision trees
during training and outputs either the mode of the classes (for classification) or the mean prediction (for regression)
of the individual trees. The algorithm improves the accuracy and robustness of predictions by averaging the results
from multiple decision trees, reducing the risk of overfitting and handling complex data with higher reliability. The
model will learn to distinguish between 'highly druggable' and 'less druggable' pockets based on the patterns it
identifies in the training data. After training, the model can classify new protein pockets as either highly druggable
or less druggable with a high degree of accuracy.

While this model will provide valuable insights into whether a protein pocket is likely to be druggable, it’s crucial to
remember that druggability is just one aspect of a protein’s potential as a drug target. Other important factors to
consider include:

Biological Relevance: The role of the protein in disease processes and whether modulating this protein will have a
therapeutic effect.
Feasibility: Practical considerations such as how easily a drug can reach the target protein in the body, and whether
the protein is expressed in the right tissues at the right levels.
Off-target effects: The potential for off-target effects and toxicity, which could arise if the protein is similar to other
essential proteins in the body.
Building the Dataset
In this tutorial we'll use the NRLD dataset which has been widely used to study the druggability. It is a comprehensive,
nonredundant data set containing crystal structures of 71 highly druggable and 44 less druggable proteins compiled by
literature search and data mining published in the paper : DrugPred: A Structure-Based Approach To Predict Protein
Druggability Developed Using an Extensive Nonredundant Data Set

The authors have only published the list of PDB code along with the labels. So, we'll first fetch the protein structure
using Biopython. The labels are 'D' for highly druggable and 'N' for less druggable protein targets.

You can also use your own dataset if you have the labels. To obtain the structure of protein from your dataset you can
refer the DeepChem tutorial: Protein Structure Prediction with ESMFold.

!pip install biopython

Collecting biopython
Downloading biopython-1.84-cp310-cp310-manylinux_2_17_x86_64.manylinux2014_x86_64.whl.metadata (12 kB)
Requirement already satisfied: numpy in /usr/local/lib/python3.10/dist-packages (from biopython) (1.25.2)
Downloading biopython-1.84-cp310-cp310-manylinux_2_17_x86_64.manylinux2014_x86_64.whl (3.2 MB)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ 3.2/3.2 MB 23.9 MB/s eta 0:00:00
Installing collected packages: biopython
Successfully installed biopython-1.84

proteins_list = ['1pwm', '1lox', '3etr', '3f1q', '3ia4', '2cl5', '1uou', '1t46', '1unl', '1q41', '2i1m', '1pmn', '1fk
labels = ['D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D', 'D',

from Bio.PDB import PDBList

from Bio.PDB import PDBParser
import os
import pandas as pd

def fetch_protein_structure(pdb_code, save_dir):

"""
Fetches the protein structure for a given PDB code and saves it to the specified directory.
Also returns the structure in a dictionary with the PDB code as the key.

Parameters:
pdb_code (str): The PDB code of the protein structure to fetch.
save_dir (str): The directory where the PDB file will be saved.

Returns:
dict: A dictionary with the PDB code as the key and the structure as the value.
"""
try:
if not os.path.exists(save_dir):
os.makedirs(save_dir)
pdbl = PDBList()
# Retrieve the PDB file and save it with a .pdb extension
pdb_file_path = pdbl.retrieve_pdb_file(pdb_code, pdir=save_dir, file_format='pdb')
new_pdb_file_path = os.path.join(save_dir, f"{pdb_code}.pdb")
os.rename(pdb_file_path, new_pdb_file_path)

# Parse the PDB file

parser = PDBParser(PERMISSIVE=1)
structure = parser.get_structure(pdb_code, new_pdb_file_path)

# Return the structure in a dictionary

return {pdb_code: structure}

except Exception as e:
print(f'Error fetching structure for PDB code {pdb_code}: {e}')
return {pdb_code: None}

Specify the save directory and fetch the protein structure

save_directory = '/content/pdb_files/'

for protein in proteins_list:

pdb_code = protein
pdb_file_path = fetch_protein_structure(pdb_code, save_directory)

Fpocket to find the binding pockets

Fpocket is a computational tool used to identify and characterize pockets on the surface of proteins. These pockets are
potential binding sites for small molecules, making fpocket a valuable tool for drug discovery and development. By
identifying and analyzing these pockets, we can better understand protein function and identify targets for drug design.
Install the requirements

!apt-get install -y build-essential git

# Clone the fpocket repository
!git clone https://github.com/Discngine/fpocket.git
%cd fpocket
!make

Reading package lists... Done

Building dependency tree... Done
Reading state information... Done
build-essential is already the newest version (12.9ubuntu3).
git is already the newest version (1:2.34.1-1ubuntu1.11).
0 upgraded, 0 newly installed, 0 to remove and 45 not upgraded.
Cloning into 'fpocket'...
remote: Enumerating objects: 11316, done.
remote: Counting objects: 100% (5152/5152), done.
remote: Compressing objects: 100% (1379/1379), done.
remote: Total 11316 (delta 3897), reused 4572 (delta 3764), pack-reused 6164
Receiving objects: 100% (11316/11316), 127.93 MiB | 21.88 MiB/s, done.
Resolving deltas: 100% (7346/7346), done.
Updating files: 100% (3895/3895), done.
/content/fpocket
cd src/qhull/ && make
make[1]: Entering directory '/content/fpocket/src/qhull'
mkdir -p bin lib
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/rbox/rbox.o src/rbox/rbox
.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/global.o s
rc/libqhull/global.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/stat.o src
/libqhull/stat.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/geom2.o sr
c/libqhull/geom2.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/poly2.o sr
c/libqhull/poly2.c
src/libqhull/poly2.c: In function ‘qh_delridge’:
src/libqhull/poly2.c:1127:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs
/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
1127 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/merge.o sr
c/libqhull/merge.c
src/libqhull/merge.c: In function ‘qh_all_merges’:
src/libqhull/merge.c:219:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/
gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
219 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull/merge.c: In function ‘qh_appendmergeset’:
src/libqhull/merge.c:322:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/
gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
322 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
src/libqhull/merge.c: In function ‘qh_mergecycle_ridges’:
src/libqhull/merge.c:2091:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs
/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
2091 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/libqhull.o
src/libqhull/libqhull.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/geom.o src
/libqhull/geom.c
src/libqhull/geom.c: In function ‘qh_projectpoint’:
src/libqhull/geom.c:897:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
897 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
src/libqhull/geom.c: In function ‘qh_setfacetplane’:
src/libqhull/geom.c:935:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
935 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/poly.o src
/libqhull/poly.c
src/libqhull/poly.c: In function ‘qh_delfacet’:
src/libqhull/poly.c:248:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
248 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull/poly.c: In function ‘qh_makenew_nonsimplicial’:
src/libqhull/poly.c:564:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
564 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull/poly.c: In function ‘qh_newfacet’:
src/libqhull/poly.c:987:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
987 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
src/libqhull/poly.c: In function ‘qh_newridge’:
src/libqhull/poly.c:1020:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/
gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
1020 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/qset.o src
/libqhull/qset.c
src/libqhull/qset.c: In function ‘qh_setfree’:
src/libqhull/qset.c:718:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
718 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull/qset.c: In function ‘qh_setnew’:
src/libqhull/qset.c:928:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
928 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/mem.o src/
libqhull/mem.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/random.o s
rc/libqhull/random.c
src/libqhull/random.c: In function ‘qh_argv_to_command’:
src/libqhull/random.c:84:6: warning: this ‘else’ clause does not guard... []8;;https://gcc.gnu.org/onlinedocs/gc
c/Warning-Options.html#index-Wmisleading-indentation-Wmisleading-indentation]8;;]
84 | }else
| ^~~~
src/libqhull/random.c:86:7: note: ...this statement, but the latter is misleadingly indented as if it were guard
ed by the ‘else’
86 | strcat(command, s);
| ^~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/usermem.o
src/libqhull/usermem.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/userprintf
.o src/libqhull/userprintf.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/io.o src/l
ibqhull/io.c
In file included from src/libqhull/libqhull.h:38,
from src/libqhull/qhull_a.h:28,
from src/libqhull/io.c:21:
src/libqhull/io.c: In function ‘qh_printfacetridges’:
src/libqhull/qset.h:138:38: warning: this ‘for’ clause does not guard... []8;;https://gcc.gnu.org/onlinedocs/gcc
/Warning-Options.html#index-Wmisleading-indentation-Wmisleading-indentation]8;;]
138 | if (((variable= NULL), set)) for (\
| ^~~
src/libqhull/libqhull.h:936:34: note: in expansion of macro ‘FOREACHsetelement_’
936 | #define FOREACHridge_(ridges) FOREACHsetelement_(ridgeT, ridges, ridge)
| ^~~~~~~~~~~~~~~~~~
src/libqhull/io.c:2622:7: note: in expansion of macro ‘FOREACHridge_’
2622 | FOREACHridge_(facet->ridges)
| ^~~~~~~~~~~~~
src/libqhull/io.c:2624:9: note: ...this statement, but the latter is misleadingly indented as if it were guarded
by the ‘for’
2624 | qh_fprintf(fp, 9185, "\n");
| ^~~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/user.o src
/libqhull/user.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/rboxlib.o
src/libqhull/rboxlib.c
In file included from /usr/include/string.h:535,
from src/libqhull/rboxlib.c:22:
In function ‘strncat’,
inlined from ‘qh_rboxpoints’ at src/libqhull/rboxlib.c:385:5:
/usr/include/x86_64-linux-gnu/bits/string_fortified.h:138:10: warning: ‘__builtin___strncat_chk’ output may be t
runcated copying between 0 and 199 bytes from a string of length 199 []8;;https://gcc.gnu.org/onlinedocs/gcc/War
ning-Options.html#index-Wstringop-truncation-Wstringop-truncation]8;;]
138 | return __builtin___strncat_chk (__dest, __src, __len,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
139 | __glibc_objsize (__dest));
| ~~~~~~~~~~~~~~~~~~~~~~~~~
src/libqhull/rboxlib.c: In function ‘qh_rboxpoints’:
src/libqhull/rboxlib.c:93:7: warning: variable ‘coincidentcount’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;
;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
93 | int coincidentcount=0, coincidenttotal=0, coincidentpoints=0;
| ^~~~~~~~~~~~~~~
src/libqhull/rboxlib.c:93:45: warning: variable ‘coincidentpoints’ might be clobbered by ‘longjmp’ or ‘vfork’ []
8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
93 | int coincidentcount=0, coincidenttotal=0, coincidentpoints=0;
| ^~~~~~~~~~~~~~~~
src/libqhull/rboxlib.c:94:30: warning: variable ‘seed’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https://g
cc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
94 | int cubesize, diamondsize, seed=0, count, apex;
| ^~~~
src/libqhull/rboxlib.c:95:7: warning: variable ‘dim’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https://gcc
.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
95 | int dim=3, numpoints=0, totpoints, addpoints=0;
| ^~~
src/libqhull/rboxlib.c:95:14: warning: variable ‘numpoints’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
95 | int dim=3, numpoints=0, totpoints, addpoints=0;
| ^~~~~~~~~
src/libqhull/rboxlib.c:95:38: warning: variable ‘addpoints’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
95 | int dim=3, numpoints=0, totpoints, addpoints=0;
| ^~~~~~~~~
src/libqhull/rboxlib.c:96:7: warning: variable ‘issphere’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:
//gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~~
src/libqhull/rboxlib.c:96:19: warning: variable ‘isaxis’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~
src/libqhull/rboxlib.c:96:30: warning: variable ‘iscdd’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https://
gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~
src/libqhull/rboxlib.c:96:39: warning: variable ‘islens’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~
src/libqhull/rboxlib.c:96:49: warning: variable ‘isregular’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~~~
src/libqhull/rboxlib.c:96:62: warning: variable ‘iswidth’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:
//gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~
src/libqhull/rboxlib.c:96:73: warning: variable ‘addcube’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:
//gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
96 | int issphere=0, isaxis=0, iscdd=0, islens=0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~
src/libqhull/rboxlib.c:97:16: warning: variable ‘isspiral’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
97 | int isgap=0, isspiral=0, NOcommand=0, adddiamond=0;
| ^~~~~~~~
src/libqhull/rboxlib.c:97:28: warning: variable ‘NOcommand’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
97 | int isgap=0, isspiral=0, NOcommand=0, adddiamond=0;
| ^~~~~~~~~
src/libqhull/rboxlib.c:97:41: warning: variable ‘adddiamond’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
97 | int isgap=0, isspiral=0, NOcommand=0, adddiamond=0;
| ^~~~~~~~~~
src/libqhull/rboxlib.c:98:7: warning: variable ‘israndom’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:
//gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
98 | int israndom=0, istime=0;
| ^~~~~~~~
src/libqhull/rboxlib.c:98:19: warning: variable ‘istime’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
98 | int israndom=0, istime=0;
| ^~~~~~
src/libqhull/rboxlib.c:99:7: warning: variable ‘isbox’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https://g
cc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
99 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~
src/libqhull/rboxlib.c:99:16: warning: variable ‘issimplex’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
99 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~~~~~
src/libqhull/rboxlib.c:99:29: warning: variable ‘issimplex2’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
99 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~~~~~~
src/libqhull/rboxlib.c:99:43: warning: variable ‘ismesh’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
99 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~~
src/libqhull/rboxlib.c:100:10: warning: variable ‘width’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
100 | double width=0.0, gap=0.0, radius=0.0, coincidentradius=0.0;
| ^~~~~
src/libqhull/rboxlib.c:100:30: warning: variable ‘radius’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:
//gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
100 | double width=0.0, gap=0.0, radius=0.0, coincidentradius=0.0;
| ^~~~~~
src/libqhull/rboxlib.c:100:42: warning: variable ‘coincidentradius’ might be clobbered by ‘longjmp’ or ‘vfork’ [
]8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
100 | double width=0.0, gap=0.0, radius=0.0, coincidentradius=0.0;
| ^~~~~~~~~~~~~~~~
src/libqhull/rboxlib.c:101:33: warning: variable ‘meshm’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
101 | double coord[MAXdim], offset, meshm=3.0, meshn=4.0, meshr=5.0;
| ^~~~~
src/libqhull/rboxlib.c:101:44: warning: variable ‘meshn’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
101 | double coord[MAXdim], offset, meshm=3.0, meshn=4.0, meshr=5.0;
| ^~~~~
src/libqhull/rboxlib.c:101:55: warning: variable ‘meshr’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
101 | double coord[MAXdim], offset, meshm=3.0, meshn=4.0, meshr=5.0;
| ^~~~~
src/libqhull/rboxlib.c:102:20: warning: variable ‘simplex’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
102 | double *coordp, *simplex= NULL, *simplexp;
| ^~~~~~~
src/libqhull/rboxlib.c:104:39: warning: variable ‘lensangle’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
104 | double norm, factor, randr, rangap, lensangle=0, lensbase=1;
| ^~~~~~~~~
src/libqhull/rboxlib.c:104:52: warning: variable ‘lensbase’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
104 | double norm, factor, randr, rangap, lensangle=0, lensbase=1;
| ^~~~~~~~
src/libqhull/rboxlib.c:105:34: warning: variable ‘cube’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https://
gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
105 | double anglediff, angle, x, y, cube=0.0, diamond=0.0;
| ^~~~
src/libqhull/rboxlib.c:105:44: warning: variable ‘diamond’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
105 | double anglediff, angle, x, y, cube=0.0, diamond=0.0;
| ^~~~~~~
src/libqhull/rboxlib.c:106:10: warning: variable ‘box’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https://g
cc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
106 | double box= qh_DEFAULTbox; /* scale all numbers before output */
| ^~~
src/libqhull/rboxlib.c:109:26: warning: variable ‘first_point’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;h
ttps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
109 | char *s= command, *t, *first_point= NULL;
| ^~~~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic/userprintf
_rbox.o src/libqhull/userprintf_rbox.c
==========================================
==== If ar fails, try make qhullx ====
==========================================
ar -rs lib/libqhullstatic.a src/libqhullstatic/global.o src/libqhullstatic/stat.o src/libqhullstatic/geom2.o src
/libqhullstatic/poly2.o src/libqhullstatic/merge.o src/libqhullstatic/libqhull.o src/libqhullstatic/geom.o src/l
ibqhullstatic/poly.o src/libqhullstatic/qset.o src/libqhullstatic/mem.o src/libqhullstatic/random.o src/libqhull
static/usermem.o src/libqhullstatic/userprintf.o src/libqhullstatic/io.o src/libqhullstatic/user.o src/libqhulls
tatic/rboxlib.o src/libqhullstatic/userprintf_rbox.o
ar: creating lib/libqhullstatic.a
#If 'ar -rs' fails try using 'ar -s' with 'ranlib'
#ranlib lib/libqhullstatic.a
gcc -o bin/rbox src/rbox/rbox.o -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -Llib -
lqhullstatic -lm
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/qdelaunay/qdelaun.o src/q
delaunay/qdelaun.c
gcc -o bin/qdelaunay src/qdelaunay/qdelaun.o -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Ws
hadow -Llib -lqhullstatic -lm
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/qhalf/qhalf.o src/qhalf/q
half.c
gcc -o bin/qhalf src/qhalf/qhalf.o -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -Lli
b -lqhullstatic -lm
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/qhull/unix_r.o src/qhull/
unix_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/global_r
.o src/libqhull_r/global_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/stat_r.o
src/libqhull_r/stat_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/geom2_r.
o src/libqhull_r/geom2_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/poly2_r.
o src/libqhull_r/poly2_r.c
src/libqhull_r/poly2_r.c: In function ‘qh_delridge’:
src/libqhull_r/poly2_r.c:1127:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/online
docs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
1127 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/merge_r.
o src/libqhull_r/merge_r.c
src/libqhull_r/merge_r.c: In function ‘qh_all_merges’:
src/libqhull_r/merge_r.c:219:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlined
ocs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
219 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull_r/merge_r.c: In function ‘qh_appendmergeset’:
src/libqhull_r/merge_r.c:322:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlined
ocs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
322 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
src/libqhull_r/merge_r.c: In function ‘qh_mergecycle_ridges’:
src/libqhull_r/merge_r.c:2090:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/online
docs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
2090 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/libqhull
_r.o src/libqhull_r/libqhull_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/geom_r.o
src/libqhull_r/geom_r.c
src/libqhull_r/geom_r.c: In function ‘qh_projectpoint’:
src/libqhull_r/geom_r.c:897:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
897 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
src/libqhull_r/geom_r.c: In function ‘qh_setfacetplane’:
src/libqhull_r/geom_r.c:935:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
935 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/poly_r.o
src/libqhull_r/poly_r.c
src/libqhull_r/poly_r.c: In function ‘qh_delfacet’:
src/libqhull_r/poly_r.c:248:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
248 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull_r/poly_r.c: In function ‘qh_makenew_nonsimplicial’:
src/libqhull_r/poly_r.c:564:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
564 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull_r/poly_r.c: In function ‘qh_newfacet’:
src/libqhull_r/poly_r.c:987:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
987 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
src/libqhull_r/poly_r.c: In function ‘qh_newridge’:
src/libqhull_r/poly_r.c:1020:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlined
ocs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
1020 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/qset_r.o
src/libqhull_r/qset_r.c
src/libqhull_r/qset_r.c: In function ‘qh_setfree’:
src/libqhull_r/qset_r.c:718:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
718 | void **freelistp; /* used if !qh_NOmem by qh_memfree_() */
| ^~~~~~~~~
src/libqhull_r/qset_r.c: In function ‘qh_setnew’:
src/libqhull_r/qset_r.c:928:10: warning: variable ‘freelistp’ set but not used []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wunused-but-set-variable-Wunused-but-set-variable]8;;]
928 | void **freelistp; /* used if !qh_NOmem by qh_memalloc_() */
| ^~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/mem_r.o
src/libqhull_r/mem_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/random_r
.o src/libqhull_r/random_r.c
src/libqhull_r/random_r.c: In function ‘qh_argv_to_command’:
src/libqhull_r/random_r.c:84:6: warning: this ‘else’ clause does not guard... []8;;https://gcc.gnu.org/onlinedoc
s/gcc/Warning-Options.html#index-Wmisleading-indentation-Wmisleading-indentation]8;;]
84 | }else
| ^~~~
src/libqhull_r/random_r.c:86:7: note: ...this statement, but the latter is misleadingly indented as if it were g
uarded by the ‘else’
86 | strcat(command, s);
| ^~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/usermem_
r.o src/libqhull_r/usermem_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/userprin
tf_r.o src/libqhull_r/userprintf_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/io_r.o s
rc/libqhull_r/io_r.c
In file included from src/libqhull_r/libqhull_r.h:32,
from src/libqhull_r/qhull_ra.h:28,
from src/libqhull_r/io_r.c:21:
src/libqhull_r/io_r.c: In function ‘qh_printfacetridges’:
src/libqhull_r/qset_r.h:143:38: warning: this ‘for’ clause does not guard... []8;;https://gcc.gnu.org/onlinedocs
/gcc/Warning-Options.html#index-Wmisleading-indentation-Wmisleading-indentation]8;;]
143 | if (((variable= NULL), set)) for (\
| ^~~
src/libqhull_r/libqhull_r.h:926:34: note: in expansion of macro ‘FOREACHsetelement_’
926 | #define FOREACHridge_(ridges) FOREACHsetelement_(ridgeT, ridges, ridge)
| ^~~~~~~~~~~~~~~~~~
src/libqhull_r/io_r.c:2622:7: note: in expansion of macro ‘FOREACHridge_’
2622 | FOREACHridge_(facet->ridges)
| ^~~~~~~~~~~~~
src/libqhull_r/io_r.c:2624:9: note: ...this statement, but the latter is misleadingly indented as if it were gua
rded by the ‘for’
2624 | qh_fprintf(qh, fp, 9185, "\n");
| ^~~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/user_r.o
src/libqhull_r/user_r.c
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/rboxlib_
r.o src/libqhull_r/rboxlib_r.c
In file included from /usr/include/string.h:535,
from src/libqhull_r/rboxlib_r.c:22:
In function ‘strncat’,
inlined from ‘qh_rboxpoints’ at src/libqhull_r/rboxlib_r.c:358:5:
/usr/include/x86_64-linux-gnu/bits/string_fortified.h:138:10: warning: ‘__builtin___strncat_chk’ output may be t
runcated copying between 0 and 199 bytes from a string of length 199 []8;;https://gcc.gnu.org/onlinedocs/gcc/War
ning-Options.html#index-Wstringop-truncation-Wstringop-truncation]8;;]
138 | return __builtin___strncat_chk (__dest, __src, __len,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
139 | __glibc_objsize (__dest));
| ~~~~~~~~~~~~~~~~~~~~~~~~~
src/libqhull_r/rboxlib_r.c: In function ‘qh_rboxpoints’:
src/libqhull_r/rboxlib_r.c:75:7: warning: variable ‘coincidentcount’ might be clobbered by ‘longjmp’ or ‘vfork’
[]8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
75 | int coincidentcount=0, coincidenttotal=0, coincidentpoints=0;
| ^~~~~~~~~~~~~~~
src/libqhull_r/rboxlib_r.c:75:45: warning: variable ‘coincidentpoints’ might be clobbered by ‘longjmp’ or ‘vfork
’ []8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
75 | int coincidentcount=0, coincidenttotal=0, coincidentpoints=0;
| ^~~~~~~~~~~~~~~~
src/libqhull_r/rboxlib_r.c:76:30: warning: variable ‘seed’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
76 | int cubesize, diamondsize, seed=0, count, apex;
| ^~~~
src/libqhull_r/rboxlib_r.c:77:7: warning: variable ‘dim’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:/
/gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
77 | int dim=3 , numpoints= 0, totpoints, addpoints=0;
| ^~~
src/libqhull_r/rboxlib_r.c:77:15: warning: variable ‘numpoints’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;
https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
77 | int dim=3 , numpoints= 0, totpoints, addpoints=0;
| ^~~~~~~~~
src/libqhull_r/rboxlib_r.c:77:40: warning: variable ‘addpoints’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;
https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
77 | int dim=3 , numpoints= 0, totpoints, addpoints=0;
| ^~~~~~~~~
src/libqhull_r/rboxlib_r.c:78:7: warning: variable ‘issphere’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;ht
tps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~~
src/libqhull_r/rboxlib_r.c:78:19: warning: variable ‘isaxis’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~
src/libqhull_r/rboxlib_r.c:78:30: warning: variable ‘iscdd’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~
src/libqhull_r/rboxlib_r.c:78:40: warning: variable ‘islens’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~
src/libqhull_r/rboxlib_r.c:78:51: warning: variable ‘isregular’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;
https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~~~
src/libqhull_r/rboxlib_r.c:78:64: warning: variable ‘iswidth’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;ht
tps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~
src/libqhull_r/rboxlib_r.c:78:75: warning: variable ‘addcube’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;ht
tps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
78 | int issphere=0, isaxis=0, iscdd= 0, islens= 0, isregular=0, iswidth=0, addcube=0;
| ^~~~~~~
src/libqhull_r/rboxlib_r.c:79:16: warning: variable ‘isspiral’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;h
ttps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
79 | int isgap=0, isspiral=0, NOcommand= 0, adddiamond=0;
| ^~~~~~~~
src/libqhull_r/rboxlib_r.c:79:28: warning: variable ‘NOcommand’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;
https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
79 | int isgap=0, isspiral=0, NOcommand= 0, adddiamond=0;
| ^~~~~~~~~
src/libqhull_r/rboxlib_r.c:79:42: warning: variable ‘adddiamond’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;
;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
79 | int isgap=0, isspiral=0, NOcommand= 0, adddiamond=0;
| ^~~~~~~~~~
src/libqhull_r/rboxlib_r.c:80:7: warning: variable ‘israndom’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;ht
tps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
80 | int israndom=0, istime=0;
| ^~~~~~~~
src/libqhull_r/rboxlib_r.c:80:19: warning: variable ‘istime’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
80 | int israndom=0, istime=0;
| ^~~~~~
src/libqhull_r/rboxlib_r.c:81:7: warning: variable ‘isbox’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
81 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~
src/libqhull_r/rboxlib_r.c:81:16: warning: variable ‘issimplex’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;
https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
81 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~~~~~
src/libqhull_r/rboxlib_r.c:81:29: warning: variable ‘issimplex2’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;
;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
81 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~~~~~~
src/libqhull_r/rboxlib_r.c:81:43: warning: variable ‘ismesh’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
81 | int isbox=0, issimplex=0, issimplex2=0, ismesh=0;
| ^~~~~~
src/libqhull_r/rboxlib_r.c:82:10: warning: variable ‘width’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
82 | double width=0.0, gap=0.0, radius=0.0, coincidentradius=0.0;
| ^~~~~
src/libqhull_r/rboxlib_r.c:82:30: warning: variable ‘radius’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;htt
ps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
82 | double width=0.0, gap=0.0, radius=0.0, coincidentradius=0.0;
| ^~~~~~
src/libqhull_r/rboxlib_r.c:82:42: warning: variable ‘coincidentradius’ might be clobbered by ‘longjmp’ or ‘vfork
’ []8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
82 | double width=0.0, gap=0.0, radius=0.0, coincidentradius=0.0;
| ^~~~~~~~~~~~~~~~
src/libqhull_r/rboxlib_r.c:83:33: warning: variable ‘meshm’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
83 | double coord[MAXdim], offset, meshm=3.0, meshn=4.0, meshr=5.0;
| ^~~~~
src/libqhull_r/rboxlib_r.c:83:44: warning: variable ‘meshn’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
83 | double coord[MAXdim], offset, meshm=3.0, meshn=4.0, meshr=5.0;
| ^~~~~
src/libqhull_r/rboxlib_r.c:83:55: warning: variable ‘meshr’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
83 | double coord[MAXdim], offset, meshm=3.0, meshn=4.0, meshr=5.0;
| ^~~~~
src/libqhull_r/rboxlib_r.c:84:20: warning: variable ‘simplex’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;ht
tps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
84 | double *coordp, *simplex= NULL, *simplexp;
| ^~~~~~~
src/libqhull_r/rboxlib_r.c:86:39: warning: variable ‘lensangle’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;
https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
86 | double norm, factor, randr, rangap, lensangle= 0, lensbase= 1;
| ^~~~~~~~~
src/libqhull_r/rboxlib_r.c:86:53: warning: variable ‘lensbase’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;h
ttps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
86 | double norm, factor, randr, rangap, lensangle= 0, lensbase= 1;
| ^~~~~~~~
src/libqhull_r/rboxlib_r.c:87:34: warning: variable ‘cube’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
87 | double anglediff, angle, x, y, cube= 0.0, diamond= 0.0;
| ^~~~
src/libqhull_r/rboxlib_r.c:87:45: warning: variable ‘diamond’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;ht
tps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
87 | double anglediff, angle, x, y, cube= 0.0, diamond= 0.0;
| ^~~~~~~
src/libqhull_r/rboxlib_r.c:88:10: warning: variable ‘box’ might be clobbered by ‘longjmp’ or ‘vfork’ []8;;https:
//gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
88 | double box= qh_DEFAULTbox; /* scale all numbers before output */
| ^~~
src/libqhull_r/rboxlib_r.c:91:26: warning: variable ‘first_point’ might be clobbered by ‘longjmp’ or ‘vfork’ []8
;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wclobbered-Wclobbered]8;;]
91 | char *s= command, *t, *first_point= NULL;
| ^~~~~~~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/libqhullstatic_r/userprin
tf_rbox_r.o src/libqhull_r/userprintf_rbox_r.c
ar -rs lib/libqhullstatic_r.a src/libqhullstatic_r/global_r.o src/libqhullstatic_r/stat_r.o src/libqhullstatic_r
/geom2_r.o src/libqhullstatic_r/poly2_r.o src/libqhullstatic_r/merge_r.o src/libqhullstatic_r/libqhull_r.o src/l
ibqhullstatic_r/geom_r.o src/libqhullstatic_r/poly_r.o src/libqhullstatic_r/qset_r.o src/libqhullstatic_r/mem_r.
o src/libqhullstatic_r/random_r.o src/libqhullstatic_r/usermem_r.o src/libqhullstatic_r/userprintf_r.o src/libqh
ullstatic_r/io_r.o src/libqhullstatic_r/user_r.o src/libqhullstatic_r/rboxlib_r.o src/libqhullstatic_r/userprint
f_rbox_r.o
ar: creating lib/libqhullstatic_r.a
#ranlib lib/libqhullstatic_r.a
gcc -o bin/qhull src/qhull/unix_r.o -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -Ll
ib -lqhullstatic_r -lm
chmod +x eg/q_test eg/q_eg eg/q_egtest
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/qconvex/qconvex.o src/qco
nvex/qconvex.c
src/qconvex/qconvex.c: In function ‘run_qconvex’:
src/qconvex/qconvex.c:72:38: warning: passing argument 5 of ‘qh_init_A’ from incompatible pointer type []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wincompatible-pointer-types-Wincompatible-pointer-type
s]8;;]
72 | qh_init_A(fin, fout, stderr, argc, argv); /* sets qh qhull_command */
| ^~~~
| |
| const char **
In file included from src/qconvex/qconvex.c:12:
src/libqhull/libqhull.h:1083:79: note: expected ‘char **’ but argument is of type ‘const char **’
1083 | void qh_init_A(FILE *infile, FILE *outfile, FILE *errfile, int argc, char *argv[]);
| ~~~~~~^~~~~~
gcc -c -O3 -ansi -Isrc -fpic -Wall -Wcast-qual -Wextra -Wwrite-strings -Wshadow -o src/qvoronoi/qvoronoi.o src/q
voronoi/qvoronoi.c
src/qvoronoi/qvoronoi.c: In function ‘run_qvoronoi’:
src/qvoronoi/qvoronoi.c:285:39: warning: passing argument 5 of ‘qh_init_A’ from incompatible pointer type []8;;h
ttps://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wincompatible-pointer-types-Wincompatible-pointer-t
ypes]8;;]
285 | qh_init_A (fin, fout, stderr, argc, argv); /* sets qh qhull_command */
| ^~~~
| |
| const char **
In file included from src/qvoronoi/qvoronoi.c:20:
src/libqhull/libqhull.h:1083:79: note: expected ‘char **’ but argument is of type ‘const char **’
1083 | void qh_init_A(FILE *infile, FILE *outfile, FILE *errfile, int argc, char *argv[]);
| ~~~~~~^~~~~~
src/qvoronoi/qvoronoi.c:237:16: warning: unused variable ‘i’ []8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-Opt
ions.html#index-Wunused-variable-Wunused-variable]8;;]
237 | int curlong, i,totlong; /* used !qh_NOmem */
| ^
make[1]: Leaving directory '/content/fpocket/src/qhull'
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/fpmain.c -o obj/fpmain.o
src/fpmain.c: In function ‘open_file_format’:
src/fpmain.c:239:16: warning: ‘pdb’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
239 | return pdb;
| ^~~
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/psorting.c -o obj/psorting.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/pscoring.c -o obj/pscoring.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/utils.c -o obj/utils.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/pertable.c -o obj/pertable.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/memhandler.c -o obj/memhandler.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/voronoi.c -o obj/voronoi.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/sort.c -o obj/sort.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/calc.c -o obj/calc.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/writepdb.c -o obj/writepdb.o
src/writepdb.c: In function ‘write_pdb_atom_line’:
src/writepdb.c:94:18: warning: comparison between pointer and integer
94 | if(insert!=NULL) {
| ^~
src/writepdb.c:101:34: warning: ‘%05x’ directive writing between 5 and 8 bytes into a region of size 6 []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
101 | sprintf(id_buf, "%05x", id);
| ^~~~
src/writepdb.c:101:33: note: directive argument in the range [100000, 2147483647]
101 | sprintf(id_buf, "%05x", id);
| ^~~~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/writepdb.h:14,
from src/writepdb.c:2:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:38:10: note: ‘__builtin___sprintf_chk’ output between 6 and 9 bytes
into a destination of size 6
38 | return __builtin___sprintf_chk (__s, __USE_FORTIFY_LEVEL - 1,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
39 | __glibc_objsize (__s), __fmt,
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
40 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
src/writepdb.c:99:34: warning: ‘%5d’ directive writing between 5 and 11 bytes into a region of size 6 []8;;https
://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
99 | sprintf(id_buf, "%5d", id);
| ^~~
src/writepdb.c:99:33: note: directive argument in the range [-2147483648, 99999]
99 | sprintf(id_buf, "%5d", id);
| ^~~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/writepdb.h:14,
from src/writepdb.c:2:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:38:10: note: ‘__builtin___sprintf_chk’ output between 6 and 12 bytes
into a destination of size 6
38 | return __builtin___sprintf_chk (__s, __USE_FORTIFY_LEVEL - 1,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
39 | __glibc_objsize (__s), __fmt,
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
40 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
src/writepdb.c:104:38: warning: ‘%4d’ directive writing between 4 and 11 bytes into a region of size 5 []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
104 | sprintf(res_id_buf, "%4d", res_id);
| ^~~
src/writepdb.c:104:37: note: directive argument in the range [-2147483648, 9999]
104 | sprintf(res_id_buf, "%4d", res_id);
| ^~~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/writepdb.h:14,
from src/writepdb.c:2:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:38:10: note: ‘__builtin___sprintf_chk’ output between 5 and 12 bytes
into a destination of size 5
38 | return __builtin___sprintf_chk (__s, __USE_FORTIFY_LEVEL - 1,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
39 | __glibc_objsize (__s), __fmt,
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
40 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
src/writepdb.c: In function ‘write_pqr_atom_line’:
src/writepdb.c:185:34: warning: ‘%05x’ directive writing between 5 and 8 bytes into a region of size 7 []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
185 | sprintf(id_buf, "%05x", id);
| ^~~~
src/writepdb.c:185:33: note: directive argument in the range [100000, 2147483647]
185 | sprintf(id_buf, "%05x", id);
| ^~~~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/writepdb.h:14,
from src/writepdb.c:2:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:38:10: note: ‘__builtin___sprintf_chk’ output between 6 and 9 bytes
into a destination of size 7
38 | return __builtin___sprintf_chk (__s, __USE_FORTIFY_LEVEL - 1,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
39 | __glibc_objsize (__s), __fmt,
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
40 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
src/writepdb.c:183:34: warning: ‘%5d’ directive writing between 5 and 11 bytes into a region of size 7 []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
183 | sprintf(id_buf, "%5d", id);
| ^~~
src/writepdb.c:183:33: note: directive argument in the range [-2147483648, 99999]
183 | sprintf(id_buf, "%5d", id);
| ^~~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/writepdb.h:14,
from src/writepdb.c:2:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:38:10: note: ‘__builtin___sprintf_chk’ output between 6 and 12 bytes
into a destination of size 7
38 | return __builtin___sprintf_chk (__s, __USE_FORTIFY_LEVEL - 1,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
39 | __glibc_objsize (__s), __fmt,
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
40 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
src/writepdb.c:188:38: warning: ‘%4d’ directive writing between 4 and 11 bytes into a region of size 6 []8;;http
s://gcc.gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
188 | sprintf(res_id_buf, "%4d", res_id);
| ^~~
src/writepdb.c:188:37: note: directive argument in the range [-2147483648, 9999]
188 | sprintf(res_id_buf, "%4d", res_id);
| ^~~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/writepdb.h:14,
from src/writepdb.c:2:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:38:10: note: ‘__builtin___sprintf_chk’ output between 5 and 12 bytes
into a destination of size 6
38 | return __builtin___sprintf_chk (__s, __USE_FORTIFY_LEVEL - 1,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
39 | __glibc_objsize (__s), __fmt,
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
40 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/rpdb.c -o obj/rpdb.o
src/rpdb.c: In function ‘rpdb_open’:
src/rpdb.c:902:42: warning: ‘z’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
902 | if (x < 9990 && y < 9990 && z < 9990)
| ~~~~~~~~~~~~~~~~~~~~~^~~~~~~~~~~
src/rpdb.c:902:30: warning: ‘y’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
902 | if (x < 9990 && y < 9990 && z < 9990)
| ~~~~~~~~~^~~~~~~~~~~
src/rpdb.c:902:20: warning: ‘x’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedocs/g
cc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
902 | if (x < 9990 && y < 9990 && z < 9990)
| ^
src/rpdb.c: In function ‘rpdb_read’:
src/rpdb.c:1234:48: warning: ‘tmpz’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
1234 | if (tmpx < 9990 && tmpy < 9990 && tmpz < 9990)
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~^~~~~~~~~~~~~~
src/rpdb.c:1234:33: warning: ‘tmpy’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
1234 | if (tmpx < 9990 && tmpy < 9990 && tmpz < 9990)
| ~~~~~~~~~~~~^~~~~~~~~~~~~~
src/rpdb.c:1234:20: warning: ‘tmpx’ may be used uninitialized in this function []8;;https://gcc.gnu.org/onlinedo
cs/gcc/Warning-Options.html#index-Wmaybe-uninitialized-Wmaybe-uninitialized]8;;]
1234 | if (tmpx < 9990 && tmpy < 9990 && tmpz < 9990)
| ^
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/tparams.c -o obj/tparams.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/fparams.c -o obj/fparams.o
src/fparams.c: In function ‘get_fpocket_args’:
src/fparams.c:296:24: warning: passing argument 1 of ‘strcpy’ from incompatible pointer type []8;;https://gcc.gn
u.org/onlinedocs/gcc/Warning-Options.html#index-Wincompatible-pointer-types-Wincompatible-pointer-types]8;;]
296 | strcpy(&residue_string, pt);
| ^~~~~~~~~~~~~~~
| |
| char * (*)[8000]
In file included from /usr/include/features.h:486,
from /usr/include/x86_64-linux-gnu/bits/libc-header-start.h:33,
from /usr/include/stdio.h:27,
from src/../headers/fparams.h:16,
from src/fparams.c:2:
/usr/include/x86_64-linux-gnu/bits/string_fortified.h:77:1: note: expected ‘char * restrict’ but argument is of
type ‘char * (*)[8000]’
77 | __NTH (strcpy (char *__restrict __dest, const char *__restrict __src))
| ^~~~~
src/fparams.c:297:23: warning: assignment to ‘char *’ from incompatible pointer type ‘char **’ []8;;https://gcc.
gnu.org/onlinedocs/gcc/Warning-Options.html#index-Wincompatible-pointer-types-Wincompatible-pointer-types]8;;]
297 | rest2 = residue_string;
| ^
src/fparams.c:304:58: warning: this statement may fall through []8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-O
ptions.html#index-Wimplicit-fallthrough=-Wimplicit-fallthrough=]8;;]
304 | par->xpocket_residue_number[pti] = (unsigned short)atoi(apt); // fprintf(stdout,
"residuenumber: %d\n", atoi(apt));
| ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~^~~~~~~~~~~~~~~~~~~~~~~~~~~
src/fparams.c:305:21: note: here
305 | case 1:
| ^~~~
src/fparams.c:306:25: warning: this statement may fall through []8;;https://gcc.gnu.org/onlinedocs/gcc/Warning-O
ptions.html#index-Wimplicit-fallthrough=-Wimplicit-fallthrough=]8;;]
306 | strncpy(&(par->xpocket_insertion_code[pti]), apt, 1);
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
src/fparams.c:307:21: note: here
307 | case 2:
| ^~~~
In file included from /usr/include/stdio.h:894,
from src/../headers/fparams.h:16,
from src/fparams.c:2:
In function ‘fprintf’,
inlined from ‘parse_clustering_method’ at src/fparams.c:631:9,
inlined from ‘parse_clustering_method’ at src/fparams.c:623:5:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:105:10: warning: ‘%s’ directive argument is null []8;;https://gcc.gn
u.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
105 | return __fprintf_chk (__stream, __USE_FORTIFY_LEVEL - 1, __fmt,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
106 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
In function ‘fprintf’,
inlined from ‘parse_distance_measure’ at src/fparams.c:646:9,
inlined from ‘parse_distance_measure’ at src/fparams.c:638:5:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:105:10: warning: ‘%s’ directive argument is null []8;;https://gcc.gn
u.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
105 | return __fprintf_chk (__stream, __USE_FORTIFY_LEVEL - 1, __fmt,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
106 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
In function ‘fprintf’,
inlined from ‘parse_distance_measure’ at src/fparams.c:646:9,
inlined from ‘parse_distance_measure’ at src/fparams.c:638:5,
inlined from ‘DEPR_get_fpocket_args’ at src/fparams.c:474:27:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:105:10: warning: ‘%s’ directive argument is null []8;;https://gcc.gn
u.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
105 | return __fprintf_chk (__stream, __USE_FORTIFY_LEVEL - 1, __fmt,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
106 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
In function ‘fprintf’,
inlined from ‘parse_clustering_method’ at src/fparams.c:631:9,
inlined from ‘parse_clustering_method’ at src/fparams.c:623:5,
inlined from ‘DEPR_get_fpocket_args’ at src/fparams.c:471:27:
/usr/include/x86_64-linux-gnu/bits/stdio2.h:105:10: warning: ‘%s’ directive argument is null []8;;https://gcc.gn
u.org/onlinedocs/gcc/Warning-Options.html#index-Wformat-overflow=-Wformat-overflow=]8;;]
105 | return __fprintf_chk (__stream, __USE_FORTIFY_LEVEL - 1, __fmt,
| ^~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
106 | __va_arg_pack ());
| ~~~~~~~~~~~~~~~~~
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/pocket.c -o obj/pocket.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/refine.c -o obj/refine.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/descriptors.c -o obj/descriptors.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/aa.c -o obj/aa.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/fpocket.c -o obj/fpocket.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/write_visu.c -o obj/write_visu.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/fpout.c -o obj/fpout.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/atom.c -o obj/atom.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/writepocket.c -o obj/writepocket.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/voronoi_lst.c -o obj/voronoi_lst.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/asa.c -o obj/asa.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/clusterlib.c -o obj/clusterlib.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/energy.c -o obj/energy.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/topology.c -o obj/topology.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/read_mmcif.c -o obj/read_mmcif.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/geom2.c -o src/qhull/src/libqhull/geom2.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/geom.c -o src/qhull/src/libqhull/geom.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/global.c -o src/qhull/src/libqhull/global.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/io.c -o src/qhull/src/libqhull/io.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/libqhull.c -o src/qhull/src/libqhull/libqhull.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/mem.c -o src/qhull/src/libqhull/mem.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/merge.c -o src/qhull/src/libqhull/merge.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/poly2.c -o src/qhull/src/libqhull/poly2.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/poly.c -o src/qhull/src/libqhull/poly.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/qset.c -o src/qhull/src/libqhull/qset.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/random.c -o src/qhull/src/libqhull/random.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/rboxlib.c -o src/qhull/src/libqhull/rboxlib.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/stat.c -o src/qhull/src/libqhull/stat.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/user.c -o src/qhull/src/libqhull/user.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/usermem.c -o src/qhull/src/libqhull/usermem.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/userprintf.c -o src/qhull/src/libqhull/userprintf.o
gcc -O -g -pg -ansi -c src/qhull/src/libqhull/userprintf_rbox.c -o src/qhull/src/libqhull/userprintf_rbox.o
LD_LIBRARY_PATH=plugins/LINUXAMD64/molfile gcc obj/fpmain.o obj/psorting.o obj/pscoring.o obj/utils.o obj/pertab
le.o obj/memhandler.o obj/voronoi.o obj/sort.o obj/calc.o obj/writepdb.o obj/rpdb.o obj/tparams.o obj/fparams.o
obj/pocket.o obj/refine.o obj/descriptors.o obj/aa.o obj/fpocket.o obj/write_visu.o obj/fpout.o obj/atom.o obj/w
ritepocket.o obj/voronoi_lst.o obj/asa.o obj/clusterlib.o obj/energy.o obj/topology.o obj/read_mmcif.o src/qhull
/src/libqhull/geom2.o src/qhull/src/libqhull/geom.o src/qhull/src/libqhull/global.o src/qhull/src/libqhull/io.o
src/qhull/src/libqhull/libqhull.o src/qhull/src/libqhull/mem.o src/qhull/src/libqhull/merge.o src/qhull/src/libq
hull/poly2.o src/qhull/src/libqhull/poly.o src/qhull/src/libqhull/qset.o src/qhull/src/libqhull/random.o src/qhu
ll/src/libqhull/rboxlib.o src/qhull/src/libqhull/stat.o src/qhull/src/libqhull/user.o src/qhull/src/libqhull/use
rmem.o src/qhull/src/libqhull/userprintf.o src/qhull/src/libqhull/userprintf_rbox.o src/qhull/src/qvoronoi/qvoro
noi.o src/qhull/src/qconvex/qconvex.o -o bin/fpocket -lm -Lplugins/LINUXAMD64/molfile plugins/LINUXAMD64/molfile
/libmolfile_plugin.a -lstdc++
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/tpmain.c -o obj/tpmain.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/tpocket.c -o obj/tpocket.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/neighbor.c -o obj/neighbor.o
LD_LIBRARY_PATH=plugins/LINUXAMD64/molfile gcc obj/tpmain.o obj/psorting.o obj/pscoring.o obj/utils.o obj/pertab
le.o obj/memhandler.o obj/voronoi.o obj/sort.o obj/calc.o obj/writepdb.o obj/rpdb.o obj/tparams.o obj/fparams.o
obj/pocket.o obj/refine.o obj/tpocket.o obj/descriptors.o obj/aa.o obj/fpocket.o obj/write_visu.o obj/fpout.o ob
j/atom.o obj/writepocket.o obj/voronoi_lst.o obj/neighbor.o obj/asa.o obj/clusterlib.o obj/energy.o obj/topology
.o obj/read_mmcif.o src/qhull/src/qvoronoi/qvoronoi.o src/qhull/src/qconvex/qconvex.o src/qhull/src/libqhull/geo
m2.o src/qhull/src/libqhull/geom.o src/qhull/src/libqhull/global.o src/qhull/src/libqhull/io.o src/qhull/src/lib
qhull/libqhull.o src/qhull/src/libqhull/mem.o src/qhull/src/libqhull/merge.o src/qhull/src/libqhull/poly2.o src/
qhull/src/libqhull/poly.o src/qhull/src/libqhull/qset.o src/qhull/src/libqhull/random.o src/qhull/src/libqhull/r
boxlib.o src/qhull/src/libqhull/stat.o src/qhull/src/libqhull/user.o src/qhull/src/libqhull/usermem.o src/qhull/
src/libqhull/userprintf.o src/qhull/src/libqhull/userprintf_rbox.o -o bin/tpocket -lm -Lplugins/LINUXAMD64/molfi
le plugins/LINUXAMD64/molfile/libmolfile_plugin.a -lstdc++
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/dpmain.c -o obj/dpmain.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/dpocket.c -o obj/dpocket.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/dparams.c -o obj/dparams.o
LD_LIBRARY_PATH=plugins/LINUXAMD64/molfile gcc obj/dpmain.o obj/psorting.o obj/pscoring.o obj/dpocket.o obj/dpar
ams.o obj/voronoi.o obj/sort.o obj/rpdb.o obj/descriptors.o obj/neighbor.o obj/atom.o obj/aa.o obj/pertable.o ob
j/calc.o obj/utils.o obj/writepdb.o obj/memhandler.o obj/pocket.o obj/refine.o obj/fparams.o obj/fpocket.o obj/f
pout.o obj/writepocket.o obj/write_visu.o obj/asa.o obj/read_mmcif.o obj/voronoi_lst.o obj/clusterlib.o src/qhul
l/src/libqhull/geom2.o src/qhull/src/libqhull/geom.o src/qhull/src/libqhull/global.o src/qhull/src/libqhull/io.o
src/qhull/src/libqhull/libqhull.o src/qhull/src/libqhull/mem.o src/qhull/src/libqhull/merge.o src/qhull/src/libq
hull/poly2.o src/qhull/src/libqhull/poly.o src/qhull/src/libqhull/qset.o src/qhull/src/libqhull/random.o src/qhu
ll/src/libqhull/rboxlib.o src/qhull/src/libqhull/stat.o src/qhull/src/libqhull/user.o src/qhull/src/libqhull/use
rmem.o src/qhull/src/libqhull/userprintf.o src/qhull/src/libqhull/userprintf_rbox.o src/qhull/src/qvoronoi/qvoro
noi.o src/qhull/src/qconvex/qconvex.o obj/energy.o obj/topology.o -o bin/dpocket -lm -Lplugins/LINUXAMD64/molfil
e plugins/LINUXAMD64/molfile/libmolfile_plugin.a -lstdc++
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/mdpmain.c -o obj/mdpmain.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/mdpocket.c -o obj/mdpocket.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/mdpbase.c -o obj/mdpbase.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/mdpout.c -o obj/mdpout.o
gcc -W -Wextra -Wwrite-strings -Wstrict-prototypes -DM_OS_LINUX -DMNO_MEM_DEBUG -O2 -g -pg -std=gnu99 -Iplugins/
include -Iplugins/LINUXAMD64/molfile -c src/mdparams.c -o obj/mdparams.o
LD_LIBRARY_PATH=plugins/LINUXAMD64/molfile gcc obj/mdpmain.o obj/mdpocket.o obj/mdpbase.o obj/mdpout.o obj/psort
ing.o obj/pscoring.o obj/mdparams.o obj/voronoi.o obj/sort.o obj/rpdb.o obj/descriptors.o obj/neighbor.o obj/ato
m.o obj/aa.o obj/pertable.o obj/calc.o obj/utils.o obj/writepdb.o obj/memhandler.o obj/pocket.o obj/refine.o obj
/fparams.o obj/fpocket.o obj/fpout.o obj/writepocket.o obj/write_visu.o obj/asa.o obj/read_mmcif.o obj/voronoi_l
st.o obj/clusterlib.o src/qhull/src/libqhull/geom2.o src/qhull/src/libqhull/geom.o src/qhull/src/libqhull/global
.o src/qhull/src/libqhull/io.o src/qhull/src/libqhull/libqhull.o src/qhull/src/libqhull/mem.o src/qhull/src/libq
hull/merge.o src/qhull/src/libqhull/poly2.o src/qhull/src/libqhull/poly.o src/qhull/src/libqhull/qset.o src/qhul
l/src/libqhull/random.o src/qhull/src/libqhull/rboxlib.o src/qhull/src/libqhull/stat.o src/qhull/src/libqhull/us
er.o src/qhull/src/libqhull/usermem.o src/qhull/src/libqhull/userprintf.o src/qhull/src/libqhull/userprintf_rbox
.o src/qhull/src/qvoronoi/qvoronoi.o src/qhull/src/qconvex/qconvex.o obj/energy.o obj/topology.o -o bin/mdpocket
-lm -Lplugins/LINUXAMD64/molfile plugins/LINUXAMD64/molfile/libmolfile_plugin.a -lstdc++

Run Fpocket for each of the protein and save the output in output directory

import subprocess
def run_fpocket(pdb_file_path):
"""
Runs fpocket on the given PDB file to find binding pockets.

Parameters:
pdb_file_path (str): The path to the PDB file.

Returns:
str: The path to the fpocket output directory.
"""
try:
# Run fpocket
command = ["bin/fpocket", "-f", pdb_file_path]
subprocess.run(command, check=True)

# Extract the output directory path

pdb_base = os.path.basename(pdb_file_path).split('.')[0]
output_dir = f"{pdb_base}_out"
except subprocess.CalledProcessError as e:
print(f'Error running fpocket on {pdb_file_path}: {e}')
return None

Specify the base directory where the pdb files are stored

base_pdb_files = '/content/pdb_files/'

Run Fpocket

for protein in proteins_list:

protein_structure = os.path.join(base_pdb_files, f'{protein}.pdb')
run_fpocket(protein_structure)

Let's have a look at the fpocket output

# We'll have a look at the protein /content/pdb_files/1ajs_out

fpocket_info_dir = '/content/pdb_files/1ajs_out/1ajs_info.txt'
with open(fpocket_info_dir, 'r') as file:
for line in file:
print(line.strip())

Pocket 1 :
Score : 0.924
Druggability Score : 0.535
Number of Alpha Spheres : 95
Total SASA : 9.960
Polar SASA : 7.544
Apolar SASA : 2.415
Volume : 493.527
Mean local hydrophobic density : 21.440
Mean alpha sphere radius : 3.774
Mean alp. sph. solvent access : 0.449
Apolar alpha sphere proportion : 0.263
Hydrophobicity score: 26.957
Volume score: 4.348
Polarity score: 14
Charge score : 4
Proportion of polar atoms: 49.020
Alpha sphere density : 5.127
Cent. of mass - Alpha Sphere max dist: 11.895
Flexibility : 0.031

Pocket 2 :
Score : 0.323
Druggability Score : 0.615
Number of Alpha Spheres : 83
Total SASA : 157.049
Polar SASA : 99.083
Apolar SASA : 57.966
Volume : 479.790
Mean local hydrophobic density : 15.053
Mean alpha sphere radius : 3.795
Mean alp. sph. solvent access : 0.423
Apolar alpha sphere proportion : 0.229
Hydrophobicity score: 21.000
Volume score: 4.100
Polarity score: 6
Charge score : 1
Proportion of polar atoms: 54.167
Alpha sphere density : 5.868
Cent. of mass - Alpha Sphere max dist: 17.292
Flexibility : 0.090

Pocket 3 :
Score : 0.308
Druggability Score : 0.848
Number of Alpha Spheres : 67
Total SASA : 172.894
Polar SASA : 69.038
Apolar SASA : 103.856
Volume : 695.777
Mean local hydrophobic density : 23.312
Mean alpha sphere radius : 3.936
Mean alp. sph. solvent access : 0.537
Apolar alpha sphere proportion : 0.478
Hydrophobicity score: 29.350
Volume score: 4.450
Polarity score: 9
Charge score : 0
Proportion of polar atoms: 37.736
Alpha sphere density : 6.774
Cent. of mass - Alpha Sphere max dist: 19.126
Flexibility : 0.087

Pocket 4 :
Score : 0.170
Druggability Score : 0.001
Number of Alpha Spheres : 37
Total SASA : 77.069
Polar SASA : 32.387
Apolar SASA : 44.682
Volume : 291.443
Mean local hydrophobic density : 5.000
Mean alpha sphere radius : 3.776
Mean alp. sph. solvent access : 0.544
Apolar alpha sphere proportion : 0.162
Hydrophobicity score: 29.100
Volume score: 3.700
Polarity score: 4
Charge score : 2
Proportion of polar atoms: 44.444
Alpha sphere density : 3.532
Cent. of mass - Alpha Sphere max dist: 9.721
Flexibility : 0.067

Pocket 5 :
Score : 0.124
Druggability Score : 0.016
Number of Alpha Spheres : 39
Total SASA : 77.117
Polar SASA : 31.227
Apolar SASA : 45.890
Volume : 303.785
Mean local hydrophobic density : 16.000
Mean alpha sphere radius : 4.001
Mean alp. sph. solvent access : 0.587
Apolar alpha sphere proportion : 0.436
Hydrophobicity score: 45.154
Volume score: 5.000
Polarity score: 4
Charge score : 1
Proportion of polar atoms: 42.857
Alpha sphere density : 2.914
Cent. of mass - Alpha Sphere max dist: 6.045
Flexibility : 0.084

Pocket 6 :
Score : 0.116
Druggability Score : 0.002
Number of Alpha Spheres : 16
Total SASA : 66.472
Polar SASA : 19.375
Apolar SASA : 47.097
Volume : 273.670
Mean local hydrophobic density : 9.000
Mean alpha sphere radius : 3.896
Mean alp. sph. solvent access : 0.607
Apolar alpha sphere proportion : 0.625
Hydrophobicity score: 32.429
Volume score: 3.714
Polarity score: 3
Charge score : -1
Proportion of polar atoms: 30.000
Alpha sphere density : 3.763
Cent. of mass - Alpha Sphere max dist: 6.233
Flexibility : 0.132

Pocket 7 :
Score : 0.100
Druggability Score : 0.006
Number of Alpha Spheres : 23
Total SASA : 55.512
Polar SASA : 20.490
Apolar SASA : 35.021
Volume : 180.286
Mean local hydrophobic density : 9.000
Mean alpha sphere radius : 3.700
Mean alp. sph. solvent access : 0.507
Apolar alpha sphere proportion : 0.435
Hydrophobicity score: 18.714
Volume score: 4.857
Polarity score: 5
Charge score : 1
Proportion of polar atoms: 38.889
Alpha sphere density : 2.712
Cent. of mass - Alpha Sphere max dist: 7.423
Flexibility : 0.082

Pocket 8 :
Score : 0.096
Druggability Score : 0.040
Number of Alpha Spheres : 46
Total SASA : 120.073
Polar SASA : 45.200
Apolar SASA : 74.873
Volume : 356.338
Mean local hydrophobic density : 15.889
Mean alpha sphere radius : 3.856
Mean alp. sph. solvent access : 0.467
Apolar alpha sphere proportion : 0.391
Hydrophobicity score: 40.909
Volume score: 4.545
Polarity score: 3
Charge score : 1
Proportion of polar atoms: 35.714
Alpha sphere density : 4.130
Cent. of mass - Alpha Sphere max dist: 9.926
Flexibility : 0.114

Pocket 9 :
Score : 0.094
Druggability Score : 0.626
Number of Alpha Spheres : 59
Total SASA : 149.738
Polar SASA : 50.713
Apolar SASA : 99.026
Volume : 515.888
Mean local hydrophobic density : 30.188
Mean alpha sphere radius : 3.879
Mean alp. sph. solvent access : 0.490
Apolar alpha sphere proportion : 0.542
Hydrophobicity score: 9.812
Volume score: 4.375
Polarity score: 8
Charge score : 2
Proportion of polar atoms: 41.667
Alpha sphere density : 4.421
Cent. of mass - Alpha Sphere max dist: 10.792
Flexibility : 0.146

Pocket 10 :
Score : 0.082
Druggability Score : 0.001
Number of Alpha Spheres : 23
Total SASA : 53.189
Polar SASA : 30.244
Apolar SASA : 22.945
Volume : 215.752
Mean local hydrophobic density : 2.000
Mean alpha sphere radius : 3.912
Mean alp. sph. solvent access : 0.482
Apolar alpha sphere proportion : 0.130
Hydrophobicity score: 18.091
Volume score: 4.182
Polarity score: 5
Charge score : -1
Proportion of polar atoms: 50.000
Alpha sphere density : 2.367
Cent. of mass - Alpha Sphere max dist: 5.442
Flexibility : 0.070

Pocket 11 :
Score : 0.067
Druggability Score : 0.005
Number of Alpha Spheres : 33
Total SASA : 98.192
Polar SASA : 49.907
Apolar SASA : 48.285
Volume : 230.851
Mean local hydrophobic density : 9.000
Mean alpha sphere radius : 3.640
Mean alp. sph. solvent access : 0.400
Apolar alpha sphere proportion : 0.303
Hydrophobicity score: 20.091
Volume score: 3.818
Polarity score: 5
Charge score : 2
Proportion of polar atoms: 50.000
Alpha sphere density : 3.626
Cent. of mass - Alpha Sphere max dist: 8.639
Flexibility : 0.149

Pocket 12 :
Score : 0.066
Druggability Score : 0.000
Number of Alpha Spheres : 18
Total SASA : 70.906
Polar SASA : 40.715
Apolar SASA : 30.191
Volume : 276.108
Mean local hydrophobic density : 3.000
Mean alpha sphere radius : 3.912
Mean alp. sph. solvent access : 0.764
Apolar alpha sphere proportion : 0.222
Hydrophobicity score: -5.625
Volume score: 4.000
Polarity score: 6
Charge score : -2
Proportion of polar atoms: 42.857
Alpha sphere density : 3.259
Cent. of mass - Alpha Sphere max dist: 6.493
Flexibility : 0.248

Pocket 13 :
Score : 0.061
Druggability Score : 0.000
Number of Alpha Spheres : 16
Total SASA : 53.881
Polar SASA : 32.144
Apolar SASA : 21.737
Volume : 207.140
Mean local hydrophobic density : 0.000
Mean alpha sphere radius : 3.859
Mean alp. sph. solvent access : 0.483
Apolar alpha sphere proportion : 0.000
Hydrophobicity score: 6.857
Volume score: 3.714
Polarity score: 4
Charge score : 0
Proportion of polar atoms: 46.667
Alpha sphere density : 2.604
Cent. of mass - Alpha Sphere max dist: 5.709
Flexibility : 0.040

Pocket 14 :
Score : 0.052
Druggability Score : 0.056
Number of Alpha Spheres : 34
Total SASA : 106.933
Polar SASA : 52.590
Apolar SASA : 54.343
Volume : 337.196
Mean local hydrophobic density : 19.000
Mean alpha sphere radius : 3.914
Mean alp. sph. solvent access : 0.594
Apolar alpha sphere proportion : 0.588
Hydrophobicity score: 16.182
Volume score: 4.182
Polarity score: 5
Charge score : 0
Proportion of polar atoms: 40.000
Alpha sphere density : 3.739
Cent. of mass - Alpha Sphere max dist: 9.922
Flexibility : 0.107

Pocket 15 :
Score : 0.049
Druggability Score : 0.001
Number of Alpha Spheres : 30
Total SASA : 105.156
Polar SASA : 68.927
Apolar SASA : 36.229
Volume : 305.590
Mean local hydrophobic density : 8.000
Mean alpha sphere radius : 3.764
Mean alp. sph. solvent access : 0.478
Apolar alpha sphere proportion : 0.300
Hydrophobicity score: 32.600
Volume score: 4.000
Polarity score: 6
Charge score : -1
Proportion of polar atoms: 44.444
Alpha sphere density : 3.793
Cent. of mass - Alpha Sphere max dist: 8.473
Flexibility : 0.126

Pocket 16 :
Score : 0.038
Druggability Score : 0.002
Number of Alpha Spheres : 26
Total SASA : 87.662
Polar SASA : 35.734
Apolar SASA : 51.928
Volume : 386.685
Mean local hydrophobic density : 6.000
Mean alpha sphere radius : 3.878
Mean alp. sph. solvent access : 0.578
Apolar alpha sphere proportion : 0.269
Hydrophobicity score: 34.875
Volume score: 4.875
Polarity score: 5
Charge score : 2
Proportion of polar atoms: 40.909
Alpha sphere density : 3.155
Cent. of mass - Alpha Sphere max dist: 8.944
Flexibility : 0.084

Pocket 17 :
Score : 0.027
Druggability Score : 0.005
Number of Alpha Spheres : 22
Total SASA : 93.222
Polar SASA : 40.087
Apolar SASA : 53.136
Volume : 316.036
Mean local hydrophobic density : 12.000
Mean alpha sphere radius : 3.913
Mean alp. sph. solvent access : 0.541
Apolar alpha sphere proportion : 0.591
Hydrophobicity score: 20.750
Volume score: 4.500
Polarity score: 6
Charge score : 0
Proportion of polar atoms: 47.619
Alpha sphere density : 3.575
Cent. of mass - Alpha Sphere max dist: 8.418
Flexibility : 0.199

Pocket 18 :
Score : 0.023
Druggability Score : 0.005
Number of Alpha Spheres : 24
Total SASA : 64.654
Polar SASA : 23.594
Apolar SASA : 41.059
Volume : 215.579
Mean local hydrophobic density : 10.000
Mean alpha sphere radius : 3.658
Mean alp. sph. solvent access : 0.416
Apolar alpha sphere proportion : 0.458
Hydrophobicity score: 50.889
Volume score: 3.889
Polarity score: 2
Charge score : 1
Proportion of polar atoms: 43.750
Alpha sphere density : 2.216
Cent. of mass - Alpha Sphere max dist: 6.211
Flexibility : 0.081

Pocket 19 :
Score : 0.004
Druggability Score : 0.000
Number of Alpha Spheres : 34
Total SASA : 97.832
Polar SASA : 50.735
Apolar SASA : 47.098
Volume : 258.882
Mean local hydrophobic density : 4.000
Mean alpha sphere radius : 3.867
Mean alp. sph. solvent access : 0.559
Apolar alpha sphere proportion : 0.147
Hydrophobicity score: 33.889
Volume score: 3.333
Polarity score: 3
Charge score : 1
Proportion of polar atoms: 45.455
Alpha sphere density : 2.835
Cent. of mass - Alpha Sphere max dist: 7.099
Flexibility : 0.045

Pocket 20 :
Score : -0.001
Druggability Score : 0.001
Number of Alpha Spheres : 21
Total SASA : 90.847
Polar SASA : 30.466
Apolar SASA : 60.381
Volume : 299.652
Mean local hydrophobic density : 9.000
Mean alpha sphere radius : 4.087
Mean alp. sph. solvent access : 0.603
Apolar alpha sphere proportion : 0.476
Hydrophobicity score: 25.750
Volume score: 4.125
Polarity score: 4
Charge score : 0
Proportion of polar atoms: 40.000
Alpha sphere density : 3.251
Cent. of mass - Alpha Sphere max dist: 7.450
Flexibility : 0.080

Pocket 21 :
Score : -0.002
Druggability Score : 0.000
Number of Alpha Spheres : 23
Total SASA : 114.955
Polar SASA : 89.595
Apolar SASA : 25.360
Volume : 358.544
Mean local hydrophobic density : 0.000
Mean alpha sphere radius : 3.920
Mean alp. sph. solvent access : 0.533
Apolar alpha sphere proportion : 0.000
Hydrophobicity score: -5.375
Volume score: 4.375
Polarity score: 7
Charge score : 2
Proportion of polar atoms: 72.727
Alpha sphere density : 4.083
Cent. of mass - Alpha Sphere max dist: 8.764
Flexibility : 0.137

Pocket 22 :
Score : -0.013
Druggability Score : 0.000
Number of Alpha Spheres : 18
Total SASA : 89.372
Polar SASA : 53.143
Apolar SASA : 36.229
Volume : 317.468
Mean local hydrophobic density : 3.000
Mean alpha sphere radius : 4.007
Mean alp. sph. solvent access : 0.567
Apolar alpha sphere proportion : 0.222
Hydrophobicity score: 26.444
Volume score: 4.000
Polarity score: 4
Charge score : 1
Proportion of polar atoms: 42.105
Alpha sphere density : 3.200
Cent. of mass - Alpha Sphere max dist: 8.017
Flexibility : 0.158

Pocket 23 :
Score : -0.015
Druggability Score : 0.000
Number of Alpha Spheres : 19
Total SASA : 98.373
Polar SASA : 62.145
Apolar SASA : 36.229
Volume : 333.904
Mean local hydrophobic density : 0.000
Mean alpha sphere radius : 4.018
Mean alp. sph. solvent access : 0.736
Apolar alpha sphere proportion : 0.053
Hydrophobicity score: 0.143
Volume score: 4.143
Polarity score: 6
Charge score : -2
Proportion of polar atoms: 50.000
Alpha sphere density : 3.504
Cent. of mass - Alpha Sphere max dist: 6.972
Flexibility : 0.329

Pocket 24 :
Score : -0.015
Druggability Score : 0.035
Number of Alpha Spheres : 36
Total SASA : 105.121
Polar SASA : 50.956
Apolar SASA : 54.165
Volume : 314.308
Mean local hydrophobic density : 20.000
Mean alpha sphere radius : 3.935
Mean alp. sph. solvent access : 0.440
Apolar alpha sphere proportion : 0.583
Hydrophobicity score: 25.700
Volume score: 4.000
Polarity score: 4
Charge score : 2
Proportion of polar atoms: 41.667
Alpha sphere density : 2.846
Cent. of mass - Alpha Sphere max dist: 8.157
Flexibility : 0.076

Pocket 25 :
Score : -0.023
Druggability Score : 0.005
Number of Alpha Spheres : 26
Total SASA : 93.656
Polar SASA : 35.690
Apolar SASA : 57.966
Volume : 305.760
Mean local hydrophobic density : 11.000
Mean alpha sphere radius : 3.949
Mean alp. sph. solvent access : 0.631
Apolar alpha sphere proportion : 0.462
Hydrophobicity score: 24.429
Volume score: 4.571
Polarity score: 4
Charge score : 1
Proportion of polar atoms: 34.783
Alpha sphere density : 2.826
Cent. of mass - Alpha Sphere max dist: 7.508
Flexibility : 0.129

Pocket 26 :
Score : -0.040
Druggability Score : 0.020
Number of Alpha Spheres : 55
Total SASA : 197.532
Polar SASA : 47.786
Apolar SASA : 149.746
Volume : 676.425
Mean local hydrophobic density : 13.375
Mean alpha sphere radius : 4.011
Mean alp. sph. solvent access : 0.557
Apolar alpha sphere proportion : 0.291
Hydrophobicity score: 14.467
Volume score: 3.800
Polarity score: 8
Charge score : -2
Proportion of polar atoms: 34.146
Alpha sphere density : 4.940
Cent. of mass - Alpha Sphere max dist: 11.982
Flexibility : 0.043

Pocket 27 :
Score : -0.089
Druggability Score : 0.000
Number of Alpha Spheres : 22
Total SASA : 121.997
Polar SASA : 68.861
Apolar SASA : 53.136
Volume : 404.828
Mean local hydrophobic density : 4.000
Mean alpha sphere radius : 4.034
Mean alp. sph. solvent access : 0.488
Apolar alpha sphere proportion : 0.227
Hydrophobicity score: -1.300
Volume score: 3.700
Polarity score: 8
Charge score : 0
Proportion of polar atoms: 52.381
Alpha sphere density : 3.501
Cent. of mass - Alpha Sphere max dist: 7.081
Flexibility : 0.056

Pocket 28 :
Score : -0.116
Druggability Score : 0.001
Number of Alpha Spheres : 16
Total SASA : 81.657
Polar SASA : 32.144
Apolar SASA : 49.513
Volume : 263.256
Mean local hydrophobic density : 7.000
Mean alpha sphere radius : 4.122
Mean alp. sph. solvent access : 0.557
Apolar alpha sphere proportion : 0.500
Hydrophobicity score: -11.833
Volume score: 5.333
Polarity score: 5
Charge score : 3
Proportion of polar atoms: 28.571
Alpha sphere density : 1.896
Cent. of mass - Alpha Sphere max dist: 5.439
Flexibility : 0.071

Now, let's find the pocket with the highest druggability score in each of the target proteins and store its features in a
DataFrame for training a model in the next step.

import re

def identify_most_druggable_pocket(pocket_df):
# Find the pocket with the highest druggability score
pocket_df['Druggability Score'] = pocket_df['Druggability Score'].astype(float)
best_pocket_df = pocket_df.loc[pocket_df['Druggability Score'].idxmax()]
best_pocket_df = pd.DataFrame(best_pocket_df).T
return best_pocket_df

def extract_features(pocket_info):
pocket_data = []
# Read the file content line by line
with open(pocket_info, 'r') as file:
current_pocket_info = {}
for line in file:
if "Pocket" in line:
if current_pocket_info:
pocket_data.append(current_pocket_info)
current_pocket_info = {'Pocket': line.strip()}
else:
if ':' in line:
key, value = line.split(':')
current_pocket_info[key.strip()] = value.strip()

# Append the last pocket information

if current_pocket_info:
pocket_data.append(current_pocket_info)

# Convert the list of dictionaries to a DataFrame

pocket_df = pd.DataFrame(pocket_data)
pocket_df.drop(columns=['Pocket'], inplace=True)
return pocket_df

pocket_dataset = {}
for protein in proteins_list:
pocket_info = f'{base_pdb_files}{protein}_out/{protein}_info.txt'
pocket_df = extract_features(pocket_info)
best_pocket_df = identify_most_druggable_pocket(pocket_df)
pocket_dataset[protein] = best_pocket_df

# Combine all dataframes into one with a new column for the keys
dataset_fpocket = pd.concat(pocket_dataset.values(), keys=pocket_dataset.keys()).reset_index(level=0).rename(columns
dataset_fpocket.rename(columns={'Key': 'pdb code'}, inplace=True)

Add the label's to the dataset

# # Set the key column as the index our dataframe from intial csv file with pdb code and labels and the dataframe we
dataset_fpocket.set_index('pdb code', inplace=True)
# dataset.set_index('pdb code', inplace=True)

# # Merge the dataframes on the index to create a datset

# dataset_fpocket = dataset_fpocket.join(dataset, how='outer')

ML model to classify the binding pockets

Here, we are using random forest algorithm to train our model. However, you are free to experiment with supervised
model for classification of your choice.

import pandas as pd
from sklearn.metrics import classification_report, accuracy_score, roc_curve, roc_auc_score
from sklearn.model_selection import train_test_split
from sklearn.preprocessing import LabelEncoder
from sklearn.ensemble import RandomForestClassifier

# Separate features and labels

X = dataset_fpocket
y = labels
label_encoder = LabelEncoder()
y_encoded = label_encoder.fit_transform(y)

# Split the data into training and testing sets

X_train, X_test, y_train, y_test = train_test_split(X, y_encoded, test_size=0.2, random_state=42)

# Initialize the Random Forest model

model = RandomForestClassifier(n_estimators=100, random_state=42)

# Train the model

model.fit(X_train, y_train)

# Make predictions on the test set

y_pred = model.predict(X_test)

# Evaluate the model

print("Accuracy:", accuracy_score(y_test, y_pred))
print("Classification Report:\n", classification_report(y_test, y_pred))

Accuracy: 0.8695652173913043
Classification Report:
precision recall f1-score support

0 0.94 0.88 0.91 17

1 0.71 0.83 0.77 6

accuracy 0.87 23
macro avg 0.83 0.86 0.84 23
weighted avg 0.88 0.87 0.87 23

# Calculate the ROC curve and AUC

y_prob = model.predict_proba(X_test)[:, 1]
fpr, tpr, thresholds = roc_curve(y_test, y_prob)
roc_auc = roc_auc_score(y_test, y_prob)
import matplotlib.pyplot as plt
# Plot the ROC curve
plt.figure()
plt.plot(fpr, tpr, color='darkorange', lw=2, label='ROC curve (area = %0.2f)' % roc_auc)
plt.plot([0, 1], [0, 1], color='navy', lw=2, linestyle='--')
plt.xlim([0.0, 1.0])
plt.ylim([0.0, 1.05])
plt.xlabel('False Positive Rate')
plt.ylabel('True Positive Rate')
plt.title('Receiver Operating Characteristic (ROC) Curve')
plt.legend(loc="lower right")
plt.show()

The model achieved an accuracy of 86.96%. The precision, recall, and F1-score were 0.94, 0.88, and 0.91 for class
1(highly druggable), and 0.71, 0.83, and 0.77 for class 1(less druggable), indicating strong performance overall but
slightly lower precision for class 1.

Classifying Your Protein's Druggability

Let's find out if your protein is highly druggable or less druggable by following these steps. Assuming you already have
the 3D structure of the protein in .pdb file format, we'll use the ML model to classify the protein pockets effectively.

1. Run Fpocket to Identify the Pockets

2. Idenitfy the pocket with highest druggable score
3. Extract the features of most druggable feature in the target
4. Use the above trained model to make a prediction

In case you do not have the 3D structure of your protein, don't worry! You have two options:

Fetch the Structure Using PDB Code: You can use the fetch_protein_structure method defined above to fetch
the structure using the PDB code of the protein.

Predict the Structure Using ESMfold: If you have the protein sequence, you can use ESMfold to obtain the structure
of the protein. For more information, you can refer to the DeepChem tutorial: Protein Structure Prediction with
ESMFold.

By following these steps, you can systematically determine the druggability of a protein pocket, combining advanced
computational tools like Fpocket with the predictive power of machine learning. This process provides a robust method
for identifying promising drug targets.

fetch_protein_structure('1mbn', '/content/1mbn/')
run_fpocket('/content/1mbn/1mbn.pdb')
output_dir = '/content/1mbn'
pdb_code = '1mbn'

target_pocket_info = f'{output_dir}{pdb_code}_out/{protein}_info.txt'
target_pocket_df = extract_features(pocket_info)
best_pocket_df = identify_most_druggable_pocket(pocket_df)
prediction = label_encoder.inverse_transform(model.predict(best_pocket_df))
print(prediction)
Downloading PDB structure '1mbn'...
['N']

The predicted label is 'N' which means protein '1mbn' isn't highly druggable. Hence, it shouldn't be used as a drug
target.

ML Resources for Druggability Assessment

Here are some useful resources to help you understand the different ML methods mentioned in this tutorial:

Supervised Learning
Regression

Understanding Decision Trees in Machine Learning

Decision Tree Regression - An In-depth Guide
Linear Regression: Introduction to Linear Regression
Linear Regression Explained
Random Forest: Random Forest in Machine Learning
Random Forest: A Complete Guide for Machine Learning

Classification

K-Nearest Neighbours Algorithm

Support Vector Machine (SVM): Introduction to Support Vector Machines
Natural Language Processing (NLP): NLP Overview
Getting Started with NLP
Bayesian Networks: Introduction to Bayesian Networks

Unsupervised Learning
Clustering

K-Means Clustering: K-Means Clustering Algorithm Explained

K-Means Clustering with Python
Hierarchical Clustering: Understanding Hierarchical Clustering
Hidden Markov Model (HMM): Introduction to Hidden Markov Models

Feel free to explore these resources as you progress through the notebook to deepen your understanding of the ML
methods used in druggability assessment.

References
1. Hopkins, A. L., & Groom, C. R. (2002). The druggable genome. Nature Reviews Drug Discovery, 1(9), 727-730. DOI:
10.1038/nrd892

2. Yu, L., Xue, L., Liu, F., Li, Y., Jing, R., & Luo, J. (2022). The applications of deep learning algorithms on in silico
druggable proteins identification. Journal of Advanced Research, 41, 219-231. DOI: 10.1016/j.jare.2022.01.009

3. Hajduk, P. J., Huth, J. R., & Tse, C. (2005). Predicting protein druggability. Drug Discovery Today, 10(23-24), 1675-
1682. DOI: 10.1016/S1359-6446(05)03624-203624-2)

4. Halgren, T. A. (2009). Identifying and characterizing binding sites and assessing druggability. Journal of Chemical
Information and Modeling, 49(2), 377-389. DOI: 10.1021/ci800324m

5. Peters, J. U. (2013). Polypharmacology–foe or friend? Journal of Medicinal Chemistry, 56(22), 8955-8971. DOI:
10.1021/jm400856t

6. Ashley, E. A. (2016). Towards precision medicine. Nature Reviews Genetics, 17(9), 507-522. DOI:
10.1038/nrg.2016.86

7. Agoni, C., Olotu, F.A., Ramharack, P. et al. Druggability and drug-likeness concepts in drug design: are biomodelling
and predictive tools having their say?. J Mol Model 26, 120 (2020). DOI: 10.1007/s00894-020-04385-6

8. Abi Hussein H, Geneix C, Petitjean M, Borrel A, Flatters D, Camproux AC. Global vision of druggability issues:
applications and perspectives. Drug Discov Today. 22, 404–415 (2017)

9. Arrowsmith, J. Phase III and submission failures: 2007-2010. Nature Reviews Drug Discovery. 10(2), 1-2 (2011)

10. Excelra. (2024). Identifying Druggable Therapeutic Targets: Unveiling Promising Avenues in Drug Discovery. Excelra
White Paper. Retrieved from https://www.excelra.com/whitepaper/identifying-druggable-therapeutic-targets-
unveiling-promising-avenues-in-drug-discovery/
11. Aguti R, Gardini E, Bertazzo M, Decherchi S and Cavalli A (2022) Probabilistic Pocket Druggability Prediction via One-
Class Learning. Front. Pharmacol. 13:870479. DOI: 10.3389/fphar.2022.870479)

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Citing this Tutorial

If you found this tutorial useful, please consider citing it as:

@manual{Bioinformatics,
title={Druggability Assessment with Fpocket and Machine Learning},
organization={DeepChem},
author={Yadav, Anamika },
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Druggablity_Assessment_with_Fpo

year={2024},
}
Protein Deep Learning
by David Ricardo Figueroa Blanco

In this tutorial we will compare protein sequences featurization such as one hot encoders and aminoacids composition.
We will use some tools of DeepChem and additional packages to create a model to predict melting temperature of
proteins ( a good measurement of protein stability )

The melting temperature (MT) of a protein is a measurement of protein stability. This measure could vary from a big
variety of experimental conditions, however, curated databases cand be found in literature
https://aip.scitation.org/doi/10.1063/1.4947493. In this paper we can find a lot of thermodynamic information of proteins
and therefore a big resource for the study of protein stability. Other information related with protein stability could be
the change in Gibbs Free Energy

due to a mutation.

The study of protein stability is important in areas such as protein engineering and biocatalysis because catalytic
efficiency could be directly related to the tertiary structure of the protein in study.

!curl -Lo conda_installer.py https://raw.githubusercontent.com/deepchem/deepchem/master/scripts/colab_install.py

import conda_installer
conda_installer.install()
!/root/miniconda/bin/conda info -e

!pip install --pre deepchem

!pip install propy3

Data extraction
In this cell, we download the dataset published in the paper https://aip.scitation.org/doi/10.1063/1.4947493 from the
DeepChem dataset repository

import deepchem as dc
import os
from deepchem.utils import download_url
data_dir = dc.utils.get_data_dir()
download_url("https://deepchemdata.s3-us-west-1.amazonaws.com/datasets/pucci-proteins-appendixtable1.csv",dest_dir=
print('Dataset Dowloaded at {}'.format(data_dir))
dataset_file = os.path.join(data_dir, "pucci-proteins-appendixtable1.csv")

Dataset Dowloaded at /tmp

A closer look of the dataset: Contains the PDBid and the respective mutation and change in thermodynamical properties
in each studied protein

import pandas as pd
data = pd.read_csv(dataset_file)
data
Unnamed: Tmexp
N PDBid Chain RESN RESwt RESmut ΔTmexp ΔΔHmexp ... ΔΔGexp(T) T Nres
0 [wt]

0 NaN 1 1aky A 8 VAL ILE -1.5 47.6 70 ... 5.0 25 220

1 NaN 2 1aky A 48 GLN GLU -1.3 47.6 60 ... 4.0 25 220

2 NaN 3 1aky A 77 THR HIS -1.1 47.6 130 ... 9.0 25 220

3 NaN 4 1aky A 110 THR HIS -4.8 47.6 165 ... 11.0 25 220

4 NaN 5 1aky A 169 ASN ASP -0.6 47.6 140 ... 9.0 25 220

... ... ... ... ... ... ... ... ... ... ... ... ... ... ...

1621 NaN 1622 5pti_m52l A 15 LYS SER -1.3 91.7 -5 ... 1.2 25 58

1622 NaN 1623 5pti_m52l A 15 LYS THR -1.1 91.7 -9 ... -3.6 25 58

1623 NaN 1624 5pti_m52l A 15 LYS VAL -6.3 91.7 4 ... 4.7 25 58

1624 NaN 1625 5pti_m52l A 15 LYS TRP -7.5 91.7 17 ... 8.5 25 58

1625 NaN 1626 5pti_m52l A 15 LYS TYR -6.6 91.7 4 ... 4.6 25 58

1626 rows × 23 columns

Here we extract a small DataFrame that only contains a unique PDBid code and its respective melting temperature

WT_Tm = data[['PDBid','Tmexp [wt]']]

WT_Tm.set_index('PDBid',inplace=True)

WT_Tm

Tmexp [wt]

PDBid

1aky 47.6

... ...

5pti_m52l 91.7

1626 rows × 1 columns

Here we create a dictionary that contains as keys, the pdbid of each protein and as values, the wild type melting
temperature

dict_WT_TM = {}
for k,v in WT_Tm.itertuples():
if(k not in dict_WT_TM):
dict_WT_TM[k]=float(v)

Here we extract proteins with mutations reported only in chain A

pdbs = data[data['PDBid'].str.len()<5]
pdbs = pdbs[pdbs['Chain'] == "A"]

pdbs[['RESN','RESwt','RESmut']]
RESN RESwt RESmut

0 8 VAL ILE

1 48 GLN GLU

2 77 THR HIS

3 110 THR HIS

4 169 ASN ASP

... ... ... ...

1604 36 GLY ALA

1605 36 GLY SER

1606 37 GLY ALA

1607 39 ARG ALA

1608 46 LYS ALA

1509 rows × 3 columns

This cell extracts the total number of mutations and changes in MT. In addition, we use a dicctionary to convert the
residue mutation in a one letter code.

alls=[]
for resnum,wt in pdbs[['RESN','RESwt','RESmut','PDBid','ΔTmexp']].iteritems():
alls.append(wt.values)
d = {'CYS': 'C', 'ASP': 'D', 'SER': 'S', 'GLN': 'Q', 'LYS': 'K',
'ILE': 'I', 'PRO': 'P', 'THR': 'T', 'PHE': 'F', 'ASN': 'N',
'GLY': 'G', 'HIS': 'H', 'LEU': 'L', 'ARG': 'R', 'TRP': 'W',
'ALA': 'A', 'VAL':'V', 'GLU': 'E', 'TYR': 'Y', 'MET': 'M'}
resnum=alls[0]
wt=[d[x.strip()] for x in alls[1]] # extract the Wildtype aminoacid with one letter code
mut=[d[x.strip()] for x in alls[2]] # extract the Mutation aminoacid with one letter code
codes=alls[3] # PDB code
tms=alls[4] # Melting temperature

print("pdbid {}, WT-AA {}, Resnum {}, MUT-AA {},DeltaTm {}".format(codes[0],wt[0],resnum[0],mut[0],tms[0]))

pdbid 1aky, WT-AA V, Resnum 8, MUT-AA I,DeltaTm -1.5

PDB Download
Here we download all the pdbs by PDBID using the pdbfixer tool

from pdbfixer import PDBFixer

from simtk.openmm.app import PDBFile

!mkdir PDBs

Using the fixer from pdbfixer we download each protein from its PDB code and fix some common problems present in
the Protein Data Bank Files. This process will take around 15 minutes and 100 Mb. The use of the PDBFixer can be found
in https://htmlpreview.github.io/?https://github.com/openmm/pdbfixer/blob/master/Manual.html . In our case, we
download the pdb file from the pdb code and perform some curation such as find Nonstandar or missing residues, fix
missing atoms

import os
import time
t0 = time.time()

downloaded = os.listdir("PDBs")
PDBs_ids= set(pdbs['PDBid'])
pdb_list = []
print("Start Download ")
for pdbid in PDBs_ids:
name=pdbid+".pdb"
if(name in downloaded):
continue
try:
fixer = PDBFixer(pdbid=pdbid)
fixer.findMissingResidues()
fixer.findNonstandardResidues()
fixer.replaceNonstandardResidues()
fixer.removeHeterogens(True)
fixer.findMissingAtoms()
fixer.addMissingAtoms()
PDBFile.writeFile(fixer.topology, fixer.positions, open('./PDBs/%s.pdb' % (pdbid), 'w'),keepIds=True)
except:
print("Problem with {}".format(pdbid))
print("Total Time {}".format(time.time()-t0))

The following function help us to mutate a sequence denoted as A###B where A is the wildtype aminoacid, ### the
position and, B the new aminoacid

import re
def MutateSeq(seq,Mutant):
'''
Mutate a sequence based on a string (Mutant) that has the notation :
A###B where A is the wildtype aminoacid ### the position and B the mutation
'''
aalist = re.findall('([A-Z])([0-9]+)([A-Z])', Mutant)

#(len(aalist)==1):
newseq=seq
listseq=list(newseq)
for aas in aalist:
wildAA = aas[0]
pos = int(aas[1]) -1
if(pos >= len(listseq)):
print("Mutation not in the range of the protein")
return None
MutAA = aas[-1]

if(listseq[pos]==wildAA):

listseq[pos]=MutAA

else:
#print("WildType AA does not match")
return None
return("".join(listseq))

The following function help us to identify a sequence of aminoacids base on PDB structures

from Bio.PDB.PDBParser import PDBParser

from Bio.PDB.Polypeptide import PPBuilder
ppb=PPBuilder()
def GetSeqFromPDB(pdbid):
structure = PDBParser().get_structure(pdbid.split(".")[0], 'PDBs/{}'.format(pdbid))
seqs=[]
return ppb.build_peptides(structure)

Some examples of the described functions : GetSeqFromPDB. Take one pdb that we previously downloaded and extract
the sequence in one letter code

import warnings; warnings.simplefilter('ignore')

test="1ezm"
print(test)
seq = GetSeqFromPDB("{}.pdb".format(test))[0].get_sequence()
print("Original Sequence")
print(seq)

1ezm
Original Sequence
AEAGGPGGNQKIGKYTYGSDYGPLIVNDRCEMDDGNVITVDMNSSTDDSKTTPFRFACPTNTYKQVNGAYSPLNDAHFFGGVVFKLYRDWFGTSPLTHKLYMKVHYGRSVEN
AYWDGTAMLFGDGATMFYPLVSLDVAAHEVSHGFTEQNSGLIYRGQSGGMNEAFSDMAGEAAEFYMRGKNDFLIGYDIKKGSGALRYMDQPSRDGRSIDNASQYYNGIDVHH
SSGVYNRAFYLLANSPGWDTRKAFEVFVDANRYYWTATSNYNSGACGVIRSAQNRNYSAADVTRAFSTVGVTCPSAL

Information about the mutation

informSeq=GetSeqFromPDB(test+".pdb")[0].__repr__()
print("Seq information",informSeq)
start = re.findall('[0-9]+',informSeq)[0]
print("Reported Mutation {}{}{}".format("R",179,"A"))
numf =179 - int(start) + 1 # fix some cases of negative aminoacid numbers

Seq information <Polypeptide start=1 end=301>

Reported Mutation R179A

Mutation in the sequence.

mutfinal = "R{}A".format(numf)
print("Real Mutation = ",mutfinal)
mutseq = MutateSeq(seq,mutfinal)
print(mutseq)

Real Mutation = R179A

AEAGGPGGNQKIGKYTYGSDYGPLIVNDRCEMDDGNVITVDMNSSTDDSKTTPFRFACPTNTYKQVNGAYSPLNDAHFFGGVVFKLYRDWFGTSPLTHKLYMKVHYGRSVEN
AYWDGTAMLFGDGATMFYPLVSLDVAAHEVSHGFTEQNSGLIYRGQSGGMNEAFSDMAGEAAEFYMAGKNDFLIGYDIKKGSGALRYMDQPSRDGRSIDNASQYYNGIDVHH
SSGVYNRAFYLLANSPGWDTRKAFEVFVDANRYYWTATSNYNSGACGVIRSAQNRNYSAADVTRAFSTVGVTCPSAL

In this for loop we extract the sequences of all proteins in the dataset. In addition we created the mutated sequences
and append the change in MT. In some cases, gaps in pdbs will cause that mutateSeq function fails, therefore this
entries will be avoided. This is an important step in the whole process because creates a final tabulated data that
contains the sequence and the Melting temperature ( our label)

information = {}
count = 1
failures=[]
for code,tm,numr,wt_val,mut_val in zip(codes,tms,resnum,wt,mut):
count += 1
seq = GetSeqFromPDB("{}.pdb".format(code))[0].get_sequence()
mutfinal="WT"
if("{}-{}".format(code,mutfinal) not in information):
informSeq=GetSeqFromPDB(code+".pdb")[0].__repr__()
start = re.findall('[-0-9]+',informSeq)[0]
if(int(start)<0):
numf =numr - int(start) # if start is negative 0 is not used as resnumber
else:
numf =numr - int(start) + 1
mutfinal = "{}{}{}".format(wt_val,numf,mut_val)
mutseq = MutateSeq(seq,mutfinal)
if(mutseq==None):
failures.append((code,mutfinal))
continue
information["{}-{}".format(code,mutfinal)]=[mutseq,dict_WT_TM[code]-float(tm)]

Deep Learning and Machine Learning Models using

proteins sequences
import deepchem as dc
import tensorflow as tf

Here we extract two list, sequences (data) and melting temperature (label)

seq_list=[]
deltaTm=[]
for i in information.values():
seq_list.append(i[0])
deltaTm.append(i[1])

max_seq= 0
for i in seq_list:
if(len(i)>max_seq):
max_seq=len(i)

Here we use a OneHotFeaturizer in order to convert protein sequences in numeric arrays

codes = ['A', 'C', 'D', 'E', 'F', 'G', 'H', 'I', 'K', 'L',
'M', 'N', 'P', 'Q', 'R', 'S', 'T', 'V', 'W', 'Y']
OneHotFeaturizer = dc.feat.OneHotFeaturizer(codes,max_length=max_seq)
features = OneHotFeaturizer.featurize(seq_list)

Note that the OneHotFeaturizer produces a matrix that contains the OneHot Vector for each sequence.

features_vector = []
for i in range(len(features)):
features_vector.append(features[i].flatten())

dc_dataset = dc.data.NumpyDataset(X=features_vector,y=deltaTm)

dc_dataset

Here we create a spliiter to perform a tran_test split of the dataset

from deepchem import splits

splitter = splits.RandomSplitter()
train, test = splitter.train_test_split(dc_dataset,seed=42)
Here we create a neuronal network using tensorflow-keras and using a loss function of "MAE" to evaluate the regression
result.

import tensorflow.keras as keras

#from keras import layers
model = tf.keras.Sequential([
keras.layers.Dense(units=32, activation='relu', input_shape=dc_dataset.X.shape[1:]),
keras.layers.Dropout(0.2),
keras.layers.Dense(units=32, activation='relu'),
keras.layers.Dropout(0.2),
keras.layers.Dense(units=1),
])

model.compile(loss='mae', optimizer='adam')

print(model.summary())

history = model.fit(
train.X, train.y,
validation_data=(test.X,test.y),
batch_size=100,
epochs=30,
)

## perform a plot of loss vs epochs

import matplotlib.pyplot as plt
history_df = pd.DataFrame(history.history)
history_df[['loss', 'val_loss']].plot()
Model: "sequential_2"
_________________________________________________________________
Layer (type) Output Shape Param #
=================================================================
dense_6 (Dense) (None, 32) 422048
_________________________________________________________________
dropout_4 (Dropout) (None, 32) 0
_________________________________________________________________
dense_7 (Dense) (None, 32) 1056
_________________________________________________________________
dropout_5 (Dropout) (None, 32) 0
_________________________________________________________________
dense_8 (Dense) (None, 1) 33
=================================================================
Total params: 423,137
Trainable params: 423,137
Non-trainable params: 0
_________________________________________________________________
None
Epoch 1/30
12/12 [==============================] - 1s 20ms/step - loss: 62.4284 - val_loss: 51.3894
Epoch 2/30
12/12 [==============================] - 0s 10ms/step - loss: 45.6483 - val_loss: 22.2757
Epoch 3/30
12/12 [==============================] - 0s 12ms/step - loss: 19.4803 - val_loss: 11.7996
Epoch 4/30
12/12 [==============================] - 0s 11ms/step - loss: 18.0858 - val_loss: 8.6031
Epoch 5/30
12/12 [==============================] - 0s 11ms/step - loss: 14.5904 - val_loss: 9.4577
Epoch 6/30
12/12 [==============================] - 0s 10ms/step - loss: 14.3444 - val_loss: 7.3325
Epoch 7/30
12/12 [==============================] - 0s 10ms/step - loss: 13.6787 - val_loss: 7.5799
Epoch 8/30
12/12 [==============================] - 0s 10ms/step - loss: 14.0674 - val_loss: 6.6186
Epoch 9/30
12/12 [==============================] - 0s 11ms/step - loss: 12.8215 - val_loss: 7.4920
Epoch 10/30
12/12 [==============================] - 0s 11ms/step - loss: 13.0748 - val_loss: 5.4614
Epoch 11/30
12/12 [==============================] - 0s 11ms/step - loss: 12.3646 - val_loss: 6.7943
Epoch 12/30
12/12 [==============================] - 0s 10ms/step - loss: 11.5250 - val_loss: 5.2098
Epoch 13/30
12/12 [==============================] - 0s 11ms/step - loss: 11.5254 - val_loss: 5.4262
Epoch 14/30
12/12 [==============================] - 0s 11ms/step - loss: 12.1312 - val_loss: 6.4607
Epoch 15/30
12/12 [==============================] - 0s 11ms/step - loss: 11.4129 - val_loss: 5.6157
Epoch 16/30
12/12 [==============================] - 0s 11ms/step - loss: 11.4406 - val_loss: 6.0425
Epoch 17/30
12/12 [==============================] - 0s 12ms/step - loss: 11.4762 - val_loss: 5.3330
Epoch 18/30
12/12 [==============================] - 0s 11ms/step - loss: 11.4820 - val_loss: 8.5933
Epoch 19/30
12/12 [==============================] - 0s 11ms/step - loss: 11.1607 - val_loss: 5.6460
Epoch 20/30
12/12 [==============================] - 0s 12ms/step - loss: 11.2637 - val_loss: 5.3362
Epoch 21/30
12/12 [==============================] - 0s 11ms/step - loss: 11.4390 - val_loss: 6.2368
Epoch 22/30
12/12 [==============================] - 0s 10ms/step - loss: 10.8070 - val_loss: 6.2875
Epoch 23/30
12/12 [==============================] - 0s 11ms/step - loss: 11.1277 - val_loss: 5.3496
Epoch 24/30
12/12 [==============================] - 0s 10ms/step - loss: 11.1626 - val_loss: 5.0670
Epoch 25/30
12/12 [==============================] - 0s 10ms/step - loss: 10.9386 - val_loss: 5.0440
Epoch 26/30
12/12 [==============================] - 0s 14ms/step - loss: 11.0402 - val_loss: 5.6448
Epoch 27/30
12/12 [==============================] - 0s 14ms/step - loss: 10.7278 - val_loss: 5.3868
Epoch 28/30
12/12 [==============================] - 0s 13ms/step - loss: 10.6073 - val_loss: 5.4149
Epoch 29/30
12/12 [==============================] - 0s 12ms/step - loss: 11.0812 - val_loss: 5.9349
Epoch 30/30
12/12 [==============================] - 0s 14ms/step - loss: 10.2336 - val_loss: 5.7489
<AxesSubplot:>
DeepChem Keras Model
Note that DeepChem Keras model allows to create a deepchem model based on the previously built model of keras. All
the information in the training can be access with model.model.history

model_dc = dc.models.KerasModel(model, dc.models.losses.L1Loss())

model_dc.fit(train)

10.399123382568359

History_df = pd.DataFrame(model_dc.model.history.history)
History_df[['loss', 'val_loss']].plot()

<AxesSubplot:>

metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)
print('test dataset R2:', model_dc.evaluate(test, [metric]))

test dataset R2: {'pearson_r2_score': 0.7125054529591869}

Examples of Classic ML models

Finally, we will compare others descriptros such as AAcomposition and Composition,transition and distribution of AA
(https://www.pnas.org/content/92/19/8700)

from propy import PyPro

In the following cell, we are creating and pyPro Object based on the protein sequence. Pypro allows us the calculation of
amino acid composition vectors
Here we create a list with the aminoacido composition vector for each sequence used in the previous model.

import numpy as np
aaComplist = []
CTDList =[]
for seq in seq_list:
Obj = PyPro.GetProDes(seq)
aaComplist.append(np.array(list(Obj.GetAAComp().values())))
CTDList.append(np.array(list(Obj.GetCTD().values())))

dc_dataset_aacomp = dc.data.NumpyDataset(X=aaComplist,y=deltaTm)
dc_dataset_ctd = dc.data.NumpyDataset(X=CTDList,y=deltaTm)

Evaluation of classical machine learning models

In the following cell we create a randomForest Regressor and the deepchem SklearnModel. As it was used in the DL
models, here we use "MAE" score to evaluate the results of the regression

from deepchem import splits

splitter = splits.RandomSplitter()
train, test = splitter.train_test_split(dc_dataset_aacomp,seed=42)
from sklearn.ensemble import RandomForestRegressor
from deepchem.utils.evaluate import Evaluator
import pandas as pd
print("RandomForestRegressor")
seed = 42 # Set a random seed to get stable results
sklearn_model = RandomForestRegressor(n_estimators=100, max_features='sqrt')
sklearn_model.random_state = seed
model = dc.models.SklearnModel(sklearn_model)
model.fit(train)
metric = dc.metrics.Metric(dc.metrics.mae_score)
train_score = model.evaluate(train, [metric])
test_score = model.evaluate(test, [metric])
print("Train score is : {}".format(train_score))
print("Test score is : {}".format(test_score))

RandomForestRegressor
Train score is : {'mae_score': 1.7916551501995608}
Test score is : {'mae_score': 3.8967191996673947}

In the following cell we create a Suport Vector Regressor and the deepchem SklearnModel. As it was used in the DL
models, here we use "MAE" score to evaluate the results of the regression

print("SupportVectorMachineRegressor")
from sklearn.svm import SVR
svr_sklearn = SVR(kernel="poly",degree=4)
svr_sklearn.random_state = seed
model = dc.models.SklearnModel(svr_sklearn)
model.fit(train)
metric = dc.metrics.Metric(dc.metrics.mae_score)
train_score = model.evaluate(train, [metric])
test_score = model.evaluate(test, [metric])
print("Train score is : {}".format(train_score))
print("Test score is : {}".format(test_score))

SupportVectorMachineRegressor
Train score is : {'mae_score': 3.275727325767219}
Test score is : {'mae_score': 4.058136267284038}

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An Introduction to Antibody Design Using Protein
Language Models
By Dhuvi Karthikeyan and Aaron Menezes
This DeepChem tutorial is designed to serve as a brief primer for antibody design via protein language models.
Antibodies are immune proteins also known as immunoglobulins that are naturally produced in the body and
bind/inactivate viruses and other pathogens. They are a valuable therapeutic and save lives in immune checkpoint
inhibitors for cancer and as neutralizing antibodies for acute viral infection. In addition, they are well known outside the
hospital walls for their ability to bind and stick to arbitrary molecular targets, a useful feature in the basic sciences and
industrial biochemical facilities.

This tutorial aims to provide a quick overview of key immunology concepts needed to understand antibody structure
and function in the broader context of the immune system. We make some assumptions with familiarity with large
language models. Take a look at our other tuorial. For the sake of brevity we provide links on non-essential topics that
point to external sources wherever possible. Follow along to learn more about the immune system, and protein
language models for guided Ab design.

Note: This tutorial is loosely based on the 2023 Nature Biotechnology paper titled "Efficient evolution of human
antibodies from general protein language models" [1] by Hie et al. We thank the authors for making their methods and
data available and accessible.

1. Immunology 101

1.1 What is the immune system?

Like other body systems such as the digestive system or the cardiovascular system, the immune system is
fundamentally a collection of specialized cells that operate together to accomplish a specific homeostatic function. The
immune system is responsible for the protection of our body's vast resources (lipids, carbodhydrates, enzymes,
proteins), especially against opportunistic threats of the outside world, such as viruses and bacteria. A very simple yet
powerful component of the immune system is the skin, which keeps what's out, out and what's in, in. However, what
happens when we get a cut/scrape or when we walk past someone who's coughing and accidentally breathe in the
droplets? Thankfully, it turns out the immune system has a whole army of highly specialized white blood cells patrolling
our blood and lymph nodes, ready to launch a multi-layered response against these and the countless other cases
where foreign objects may enter our bodies. Through these white bloods cells, the immune system is able to accomplish
its primary function, self-nonself discrimination, the accurate identification of molecules that are sufficiently
dissimilar than those derived from a healthy person.

If you would like to learn more about the complex problem of self non-self discrimination, and appreciate the theory
behind the immune system's organization and function, we recommend checking out the following works:

A Theory of Self-Nonself Discrimination [2]

The common sense of the self-nonself discrimination, 2005 [3]
Conceptual aspects of self and nonself discrimination, 2011 [4]
Self-Nonself Discrimination due to Immunological Nonlinearities: the Analysis of a Series of Models by Numerical
Methods, 1987 [5]
A biological context for the self-nonself discrimination and the regulation of effector class by the immune system,
2005 [6]

1.2 Innate vs. Adaptive Immune System

Remarkably, these white blood cells operate independently, adding and subtracting from the local context (tissue
microenvironment), orchestrating cohesive responses in a completely decentralized manner. Individual white blood cells
interact with their environments through general cytokine and chemokine surface receptors that facilitate gradient
sensing of the local environment. This is the primary axis by which immune cells are able to home to sites of
infection/wound healing and send pro-inflammatory or anti-inflammatory signals to neighboring cells. In addition, nearly
all immune cells require some level of activation by means of receptor:ligand stimulation by non-self signatures. How
specific these receptors are helps highlight the delineation between the two arms of the immune system: the innate and
adaptive immune systems.

1.2.1 The Innate Immune System

The innate immune system is the body's first line of defense, and encompasses different types of cells (and proteins)
that recognize broadly non-self signals known as pathogen-associated or damage-associated molecular patterns (PAMPs
or DAMPs). The effector cells of the innate immune system are decorated with ~20 different kinds of pattern recognition
receptors (PRRs) that recognize broad signals (single stranded DNA, LPS, other signals of pathogen activity). Being the
first responders, the innate immune system handles containment, engulfing the offending signals and otherwise
blocking it off, and tries to destroy the threat. Lastly, these cells simultaneously sound the alarm, putting the local area
into a heightened state of threat detection and infection prevention, such as spiking a fever and initiating swelling to
draw in more immune cells.

1.2.2 The Adaptive Immune System

The adaptive immune system on the other hand, is slow to respond and is often brought in by innate cell activation.
Instead of broad PRRs, it relies on tens of millions of somatically rearranged and stochastically generated highly specific
adaptive immune receptors (AIRs) whose shape complementarity allows them to identify their complementary
molecular patterns called epitopes. There are many more differences between the innate and adaptive immune
systems, such as the latter's ability to develop a durable memory response, and those are introduced in greater detail
here [7]. It is important to note however, that it is through the independent and asynchronous operation of both the
innate and adaptive immune system that we see the dynamics [8] of threat detection, message passing, calling for
reinforcements, homing of adaptive immune cells, and activation/expansion of these cells, resulting in complete
clearance of the pathogen.Another key distinction between the innate and adaptive immune system is the formation of
a robust memory response. Amazingly, evolution has steered this system to imprint past pathogen exposures so that
upon re-exposure to the same signal, a small pool of memory cells is activated and antigen-specifc adaptive immune
cells rapidly proliferatre and clear the antigen-source [9].

algorithmic
Adaptive Immune Algorithm

1. Nascent progenitor cells undergoes somatic recombination to stochastically generate an

Adaptive Immune Receptor (AIR).
2. Self-selecting methods of ensuring self-tolerance remove cells that react too strongly to
the self before being released into the blood.
3. In periphery, naive (antigen-inexperienced) cells interact with antigens via AIRs in search
of their cognate epitope.
4. Upon recognition of a sufficiently strong epitope reaction, they divide rapidly and
overwhelm the offending antigen with sheer numbers and specialized effector function.
5. After the threat has cleared, this expanded population contracts as cells die without
activation signalling, and a lasting pool of memory cells remains.
6. Memory pool persists and is reactivated in an effector state upon antigen reintroduction.

1.2.3 Effector Cells of the Adaptive Immune System

There are two major types of effector cells in the adaptive immune response: T-cells and B-cells. Both the T-cell and B-
cell populations in the body are contextualized through their adaptive immune receptors, T-cell Receptors (TCRs) and B-
cell Receptors (BCRs), respectively. We can think of both populations as repertoires of receptors, conferring protection
against the threats recognized by the repertoire. T-cells help maitnain cellular immunity by interrogating the
intracellular component of our bodies' by using their TCRs to scan recycled protein fragments presented at the cell
surface (Read more about T-cell mediated immunity here [10]). B-cells, on the other hand, use their BCRs to survey the
extracellular compartment and are tasked with upkeeping humoral immunity: neutralizing threats floating around in the
blood and plasma. As effector cells of the adaptive immune response, both T-cell and B-cells are similar in their
development and their operation as a unit, though the specifics of per cell function are quite different.

Note: A helpful distinction between antigens and epitopes is that an antigen is something that broadly generates an
immune response and can have multiple epitopes. Epitopes are specific molecular patterns that have a matching
paratope (binding surface of an adaptive immune receptor).
Image Source: Creative Diagnostics

1.3 B-Cells and Antibodies

B-cells, or B-lymphocytes, get their name not from their origin in the bone marrow, but from their discovery in a
particular organ of the chicken[11]. These cells circulate in the bloodstream, equipped with unique B-cell receptors
(BCRs) that allow them to recognize specific antigens, leading to their activation. This process often requires additional
stimulation from helper T-cells which provide essential co-stimulatory signals, an additional layer of verification for non-
selfness.

Over the course of the COVID pandemic, whether we wanted to or not were exposed to the concept of antibodies and
learned of their association with some sort of protective capacity against SARS-COV-2. But what are they, and where do
they originate from?

Antibodies (Abs) are typically represented as Y-shaped proteins that bind to their cognate epitope surfaces with high
specificity and affinity, similar to how TCRs and BCRs bind to their epitopes. This is because antibodies are the soluble
form of the B-cell receptor that is secreted into the blood upon B-cell activation in the presence of its cognate antigen.
The secretion of large amounts of antibodies is the primary effector function of B-cells. Upon activation, a B-cell will
divide, with the daughter cells inheriting the same BCR, and some of these cells will differentiate into plasma cells,
which are the Ab factories capable of secreting thousands of Abs/min. This is especially useful upon antigen re-
encounter where a large amount of antibodies are released by memory cells which neutralize the pathogen even before
we develop the symptoms of infection (this is what most common vaccines are designed to do).

Image Source: Beckman

Neutralizing mechanisms of pathogenesis is only one way that antibody tagging is useful to immune defense. Antibody
tagging plays a key role in a number of humoral immunity processes:

1. Neutralization: De-activation of pathogenic function by near complete coating of the functional component of
pathogens or toxins by antibodies to inhibit interaction with host cells (i.e. and antibody that binds to the surface
glycoproteins on SARS-COV2 now inhibit that virus particle's ability to enter cells expressing ACE2).

2. Opsonization: Partial coating of pathogens enhances rates phagocytosis and removal from the blood by cells of the
innate immune system.

3. Agglutination/Precipitation): Since antibodies have 2 arms (each arm of the Y), they can cross-link and form
anitbody-antigens chains which can precipitate out of the plasma and increase their chances of being recognized as
aberrant and cleared by phagocytes.

4. Complement Activation: The complement system is a collection of inactive proteins and protein precursors are self-
amplifying on activation and help with multiple aspects of humoral immunity. Yet another function of antibodies is
their role in initiating the complement cascade that ends in the lysis or phagocytosis of pathogens.
Image Source: The Immune System: Innate and Adaptive Body Defenses Figure 21.15 pulled from [Source]

Given the importance of B-cell mediated immunity, as operationalized by the body's antibody repertoire, it's clear that
the diversity of BCR clones plays a critical role in our ability to mount an effective response against a pathogen. The
maintenance of a robust BCR repertoire highlights not only the complexity of the immune response but also underscores
the potential for leveraging the modularity of this mechanism to introduce new clones for their extraordinary precision
in therapeutics such as vaccine development.

1.4 Antibody Sequence, Structure, and Function

The remarkable diversity of antibodies is achieved through somatic recombination, or gene rearrangement at the DNA
level that occurs outside of meiosis. The AIR-specific somatic recombination is known as V(D)J recombination and
generates both TCR and BCR diversity. During V(D)J recombination, a single gene per set is sampled from the set of
variable (V), diversity (D), and joining (J) gene segments and randomly joined together with some baked in error
(insertions) to create stable BCRs with unique antigen-binding sites. Additionally, B-cells have an additional process that
further amplifies the diversity as well as the functional capacity of antigen-specific antibodies. This process is known as
somatic hypermutation. When an activated B-cell divides, somatic hypermutation (SHM) introduces point mutations in
the variable regions of BCR generating minor variants of each BCR. These daughter cells compete for survival signals
mediated through antigen binding such that only the stronger binders survive.

Structurally, antibodies are composed of two identical light chains and two identical heavy chains, linked by disulfide
bonds. Each chain contributes to the formation of the antigen-binding site, located in the variable regions. Within these
regions, hypervariable loops known as complementarity determining regions (CDRs) dictate the specificity and affinity of
the antibody-antigen interaction. This specificity is measured in terms of affinity using the dissociation constant (Kd),
and the avidity (affinity over multi-valent binding sites, see IgM, IgA). The antibody molecule is divided into two main
functional regions:

1. Fab Region (Fragment, antigen-binding): Contains the variable regions of the light and heavy chains, responsible for
antigen recognition and binding.
2. Fc Region (Fragment, crystallizable): Composed of the constant regions of the heavy chains, mediates interactions
with innate immune cells and the complement system.
Image Source: Dianova: Antibody Structure \

By harnessing the selection of evolutionary pressures during somatic hypermutation, the B-cell compartment uses a
powerful method of further tuning the antibody specificity to have some of the highest affinity interactions in the known
protein universe [12]. Their high precision and binding affinities have caused their broad adoption in not only
therapeutics but commercial and research applications as well as to tag proteins in solution in flow cytometry, CyTOF,
immuno-precipitation, and other target identification assays.

1.5 Current Paradigms for Antibodies as a Therapeutic Modality

Given their unparalleled ability to precisely and durably bind arbitrary targets, there has been a significant interest in
possessing antibodies for desired targets. There are a number of therapeutic use cases for these antibodies, for
diseases ranging from transplant rejection, non-Hodgkin's lymphoma, immune checkpoint inhibitors for cancer
immunotherapy, psoriasis, multiple sclerosis, Crohn's disease, and many more. While antibodies against common
pathogens can be isolated from the serum of convalescent individuals and screened for specificity, the process of
procuring novel antibodies is substantially more challenging and involves inoculating an animal with an antigen and
isolating the antibodies after. For example, anti-venom is a solution of antibodies derived from animals (typically horses)
against cytotoxic proteins found in venom. This procedure is both resource and labor intensive. This is because after
inoculation and isolation of antibodies from the animal, there is an additional step of screening them for reactivity
against the target using reaction chemistry methods such as surface plamon resonance or bio-layer interferometry. As
such there has been a great deal of interest in methods of in-silico antibody design. A number of approaches have
shown reasonable degrees of success in this task from guided evolution based approaches [1] to newer diffusion based
[13] approaches. In this tutorial we will pay homage to the former.

2. Let's Code! Designing Antibodies via Directed Evolution

2.1 Overview
Now that we have the minimal backgrounded needed to understand the antibody design proble and the necessary
language model background, we can jump right into antibody design via directed evolution, as shown in the figure
below:

\
Image Source: Figure 1. Outeiral et. al

2.2 Setup/Methodology
In Hie et al. the authors decide to use a general protein language model instead of one trained specifically on antibody
sequences. They use the ESM-1b and ESM-1v models which were trained on UniRef50 and UniRef90 [14], respectively.
For their directed evolution studies they select seven therapeutic antibodies associated with viral infection spanning
Influenza, Ebolavirus, and SARS-COv2. The authors use a straightforward and exhaustive mutation scheduler in
mutating every residue in the antigen binding region to every other residue and computing the likelihood of the
sequence. Sequences with likelihoods greater than or equal to the WT sequence were kept for experimental validation.
For our purposes, we need not be as thorough and can use a slightly expedited method by taking the top-k mutations at
a specific point.

Inspired by the work of Hie et al., we first define the pLM driven directed evolution task as simply passing in a masked
antibody sequence to a pLM that was previously trained on the masked language modeling objective and examining the
token probabilities for the masked amino acids. It really is that easy!

For reference we break the task down into the following steps:

# Antibody Design via pLM Directed Evolution

1. Select a pre-trained model language model (can be pre-trained on all domains or exclusively
antibodies)
2. Choose an antibody to mutate.
3. Determine the amino acid(s) to mask out*.
4. Pass the tokenized sequences into the pLM
5. Sample tokens according to a heuristic for increased fitness

*Modification of antibodies needs to focus only on the variable regions as the amino acids at the interface are the ones
responsible for driving affinity. Making edits to the constant region would actually be detrimental to antibodies' effector
function in the complement system as well as potentially disrupt binding to innate immune receptors. \

2.2.1 Loading the Model + Tokenizer

For this exploration, we pay homage to an early Antibody Language Model AbLang [15]. AbLang is a masked language
model based on the RoBERTa [16] model, and pre-trained on antibody sequences from the [observed antibody space
(OAS) [17]. AbLang consists of two models, one trained on the heavy chain sequences and one trained on the light chain
sequences and the authors demonstrate its usefulness over broader protein language models such as ESM-1b,
contradicting the findings put forth in Hie et al. Both the heavy and light chain models are identical in architecture with
a

of 768, max position embedding of 160, and 12 transformer block layers, totaling ~86M parameters.

from transformers import AutoModel, AutoTokenizer, AutoModelForMaskedLM

# Get the tokenizer

tokenizer = AutoTokenizer.from_pretrained('qilowoq/AbLang_light')

# Get the light chain model

mlm_light_chain_model = AutoModelForMaskedLM.from_pretrained('qilowoq/AbLang_light')
# Get the heavy chain model
mlm_heavy_chain_model = AutoModelForMaskedLM.from_pretrained('qilowoq/AbLang_heavy')

# Lets take a look at the model parameter count and architecture

n_params = sum(p.numel() for p in mlm_heavy_chain_model.parameters())
print(f'The Ablang model has {n_params} trainable parameters. \n')
mlm_heavy_chain_model

The Ablang model has 85809432 trainable parameters.

RobertaForMaskedLM(
(roberta): RobertaModel(
(embeddings): RobertaEmbeddings(
(word_embeddings): Embedding(24, 768, padding_idx=21)
(position_embeddings): Embedding(160, 768, padding_idx=21)
(token_type_embeddings): Embedding(2, 768)
(LayerNorm): LayerNorm((768,), eps=1e-12, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(encoder): RobertaEncoder(
(layer): ModuleList(
(0-11): 12 x RobertaLayer(
(attention): RobertaAttention(
(self): RobertaSelfAttention(
(query): Linear(in_features=768, out_features=768, bias=True)
(key): Linear(in_features=768, out_features=768, bias=True)
(value): Linear(in_features=768, out_features=768, bias=True)
(dropout): Dropout(p=0.1, inplace=False)
)
(output): RobertaSelfOutput(
(dense): Linear(in_features=768, out_features=768, bias=True)
(LayerNorm): LayerNorm((768,), eps=1e-12, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)
)
)
(intermediate): RobertaIntermediate(
(dense): Linear(in_features=768, out_features=3072, bias=True)
(intermediate_act_fn): GELUActivation()
)
(output): RobertaOutput(
(dense): Linear(in_features=3072, out_features=768, bias=True)
(LayerNorm): LayerNorm((768,), eps=1e-12, elementwise_affine=True)
(dropout): Dropout(p=0.1, inplace=False)

)
)
)
)
)
(lm_head): RobertaLMHead(
(dense): Linear(in_features=768, out_features=768, bias=True)
(layer_norm): LayerNorm((768,), eps=1e-12, elementwise_affine=True)
(decoder): Linear(in_features=768, out_features=24, bias=True)
)
)

2.2.2 Example Antibody Sequence

Next let's choose a heavy chain and light chain for designing. These were chosen from the Ablang examples page on
HuggingFace,

# Lets take the variable regions of the heavy and light chains

heavy_chain_example = 'EVQLQESGPGLVKPSETLSLTCTVSGGPINNAYWTWIRQPPGKGLEYLGYVYHTGVTNYNPSLKSRLTITIDTSRKQLSLSLKFVTAADSAVY
light_chain_example = 'GSELTQDPAVSVALGQTVRITCQGDSLRNYYASWYQQKPRQAPVLVFYGKNNRPSGIPDRFSGSSSGNTASLTISGAQAEDEADYYCNSRDSSS

2.2.3 Masking the Sequence

One of the crucial parameters with this approach is in the determination of which residues to mask and re-design. Let's
start off by first setting up some reproducible code so that we can apply the masking procedure to any number of
sequences at arbitrary points.

# Sequnece masking convenience function

def mask_seq_pos(sequence: str,
idx: int,
mask='[MASK]'):
'''Given an arbitrary antibody sequence with and a seqeunce index,
convert the residue at that index into the mask token.

'''
cleaned_sequence = sequence.replace(' ', '') # Get ride of extraneous spaces if any
assert abs(idx) < len(sequence), "Zero-indexed value needs to be less than sequence length minus one."
cleaned_sequence = list(cleaned_sequence) # Turn the sequence into a list
cleaned_sequence[idx] = '*' # Mask the sequence at idx
masked_sequence = ' '.join(cleaned_sequence) # Convert list -> seq
masked_sequence = masked_sequence.replace('*', mask)
return masked_sequence

# Test
assert mask_seq_pos('CAT', 1)=='C [MASK] T'
#TODO: Add unit tests with pytest where you can check that the assert has been hit

2.2.3 Model Inference

### Step 1. Mask the light_chain sequence

mask_idx = 9
masked_light_chain = mask_seq_pos(light_chain_example, idx=mask_idx)
### Step 2. Tokenize
tokenized_input = tokenizer(masked_light_chain, return_tensors='pt')
### Step 3. Light Chain Model
mlm_output = mlm_light_chain_model(**tokenized_input)
### Step 4. Decode the outputs to see what the model has placed
decoded_outs = tokenizer.decode(mlm_output.logits.squeeze().argmax(dim=1), skip_special_tokens=True)
print(f'Model predicted: {decoded_outs.replace(" ", "")[9]} at index {mask_idx}')
print(f'Predicted Sequence: {decoded_outs.replace(" ", "")}')
print(f'Starting Sequence: {light_chain_example}')

Model predicted: S at index 9

Predicted Sequence: SADSSSCGVSSTVAHGQTLKINSQGQRHSLYYVRWYQQKPGLAPLLLIYGKNSRPSGIPDRFSGSKSGTTASLTITGLQAEDEADYYCQQSG
GSGGHLTVGGGALLATLTQ
Starting Sequence: GSELTQDPAVSVALGQTVRITCQGDSLRNYYASWYQQKPRQAPVLVFYGKNNRPSGIPDRFSGSSSGNTASLTISGAQAEDEADYYCNSRDS
SSNHLVFGGGTKLTVLSQ

2.2.4 HuggingFace Pipeline Object

Hold on, given the tokenized input with only one masked token, we would expect to see only one change to the the
sequence. However, what we get back is something a lot more different that what we put in. Luckily, there's something
in the HuggingFace software suite that we can use to address this: Pipelines

HuggingFace Pipelines:

1. Pipeline object is a wrapper for inference and can be treated like an object for API calls
2. There is a fill-mask pipeline that we can use which accepts a single mask token in out input and outputs a dictionary
of the score of that sequence, the imputed token, and the reconstructed full sequence.

Lets see it in action:

from transformers import pipeline

filler = pipeline(task='fill-mask', model=mlm_light_chain_model, tokenizer=tokenizer)
filler(masked_light_chain) # fill in the mask

[{'score': 0.13761496543884277,
'token': 7,
'token_str': 'S',
'sequence': 'G S E L T Q D P A S S V A L G Q T V R I T C Q G D S L R N Y Y A S W Y Q Q K P R Q A P V L V F Y
G K N N R P S G I P D R F S G S S S G N T A S L T I S G A Q A E D E A D Y Y C N S R D S S S N H L V F G G G T K
L T V L S Q'},
{'score': 0.1152879148721695,
'token': 6,
'token_str': 'E',
'sequence': 'G S E L T Q D P A E S V A L G Q T V R I T C Q G D S L R N Y Y A S W Y Q Q K P R Q A P V L V F Y
G K N N R P S G I P D R F S G S S S G N T A S L T I S G A Q A E D E A D Y Y C N S R D S S S N H L V F G G G T K
L T V L S Q'},
{'score': 0.0989701896905899,
'token': 9,
'token_str': 'N',
'sequence': 'G S E L T Q D P A N S V A L G Q T V R I T C Q G D S L R N Y Y A S W Y Q Q K P R Q A P V L V F Y
G K N N R P S G I P D R F S G S S S G N T A S L T I S G A Q A E D E A D Y Y C N S R D S S S N H L V F G G G T K
L T V L S Q'},
{'score': 0.08586061000823975,
'token': 14,
'token_str': 'A',
'sequence': 'G S E L T Q D P A A S V A L G Q T V R I T C Q G D S L R N Y Y A S W Y Q Q K P R Q A P V L V F Y
G K N N R P S G I P D R F S G S S S G N T A S L T I S G A Q A E D E A D Y Y C N S R D S S S N H L V F G G G T K
L T V L S Q'},
{'score': 0.07652082294225693,
'token': 8,
'token_str': 'T',
'sequence': 'G S E L T Q D P A T S V A L G Q T V R I T C Q G D S L R N Y Y A S W Y Q Q K P R Q A P V L V F Y
G K N N R P S G I P D R F S G S S S G N T A S L T I S G A Q A E D E A D Y Y C N S R D S S S N H L V F G G G T K
L T V L S Q'}]

Congratulations you have now designed 5 new antibodies!

Disclaimer: For a more thorough antibody (re)design, we will typically want to follow an approach like what was done in
Hie et al. where every point along the sequence will be mutated and the total number of sequences will be collated and
scored with the top-100 or so antibodies being expressed for validation. If you would like to explore this feel free to try it
out yourself as a challenge!
You can also refer to the real data in Hie et al. to see if any of the predicted ones were found to work well and increase
fitness.

2.3 Limitations
While promising, this approach is obviously not without its shortcomings. Key limitations include:

Fixed length antibody design since masked tokens are applied in a 1:1 fashion.
Lack of target information included during conditional sampling step which can influence choice of amino acid given
the sequence context.
Approach is sensitive to choice of protein language model

This letter [18] provides a great synopsis of Hie et al.'s work, which by extension apply to the methods presented in this
tutorial as well.

Citing this Tutorial

If you found this tutorial useful, please consider citing it as:

@manual{Bioinformatics,
title={An Introduction to Antibody Design Using Protein Language Models},
organization={DeepChem},
author={Karthikeyan, Dhuvarakesh and Menezes, Aaron},
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/DeepChem_AntibodyTutorial_Simpl

year={2024},
}

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[3] Cohn, M. The common sense of the self-nonself discrimination. Springer Semin Immun 27, 3–17 (2005).
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[5] ROB J. DE BOER, PAULINE HOGEWEG, Self-Nonself Discrimination due to Immunological Nonlinearities: the Analysis
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[9] Shittu, A. (n.d.). Understanding immunological memory. ASM.org. https://asm.org/articles/2023/may/understanding-

immunological-memory

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[11] Glick, B., Chang, T. S., & Jaap, R. G. (1956). The Bursa of Fabricius and Antibody Production. Poultry Science, 35(1),
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[12] Nooren, I. M. (2003). NEW EMBO MEMBER’S REVIEW: Diversity of protein-protein interactions. EMBO Journal, 22(14),
3486–3492. https://doi.org/10.1093/emboj/cdg359

[13] Karolis Martinkus, Jan Ludwiczak, Kyunghyun Cho, Wei-Ching Liang, Julien Lafrance-Vanasse, Isidro Hotzel, Arvind
Rajpal, Yan Wu, Richard Bonneau, Vladimir Gligorĳevic, & Andreas Loukas. (2024). AbDiffuser: Full-Atom Generation of
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https://doi.org/10.1038/s41587-023-01991-6
Protein Language Models (Intuition): A First Look
at Modeling Syntax and Semantics of the Known
Protein Universe
By Dhuvi Karthikeyan, Aaron Menezes, Elisa Gómez de Lope, and Rakshit Singh

Inspired by the success of Large Language Models (LLMs) such as BERT, T5, and GPT, that have demonstrated state of
the art performance on sentiment analysis, summarization, question answering, and classification tasks, protein
language models (pLMs) have demonstrated similar sweeping success across a broad array of protein specific tasks.
These tasks include contact prediction, mutational landscape fitness prediction, binding site prediction, property
prediction, and much more! In this tutorial, we explore the fundamental intuition driving the success of protein language
models, by developing a strong intuition of what is actually happening under the hood and the resulting pros and cons
of their usage. If you'd like to learn more about language models in various other domains, check out DeepChem's very
own ChemBERTa, a large language model trained on the chemical domain here.

Open in Colab

Table of Contents:
1. Introduction
2. What is a language model?
3. Methods for learning language
4. How do Protein Language Models (pLMs) work?
5. MSA-aware vs non-MSA-aware protein language models
6. Evolutionary statistics of Hemoglobin and its ProtBERT learned representation
7. Concluding thoughts

1. Introduction
This DeepChem tutorial is designed to serve as an introductory primer on protein language models, a powerful and
versatile method of processing protein sequence information inspired by methods from the natural language space.
Over the past decade, natural language processing has shown the strength of using learned representations to
encapsulate the semantic meaning of text data. Notable models like word2vec [1] and GloVe [2] proved that self-
supervised pre-training on large, unlabeled corpora effectively creates robust feature embeddings that maintain
similarity and analogy in language. However, these models were limited in utility by their context-free embeddings. The
advent of context-aware models, starting with BERT [3], led to numerous sequence models applicable beyond language
domains. In biology, self-supervised pre-training on protein language models has achieved state-of-the-art performance
in various tasks by deriving context-aware amino acid embeddings that can be finteuned to capture information on
structure [4] and function [5] of proteins.

This tutorial aims to provide an overview of the concepts and intuition of protein language models that are needed to
work with them and understand their input/outputs, strengths, failure modes. We skip over the detailed breakdown of
their architecture, but invite the community to add content as they see fit in the form of a pull request to build upon
this.

Disclaimer: For brevity sake, we make some assumptions with familiarity to the multi-layered perceptron, neural
networks, and learning by gradient descent. Additionally we assume some fluency with probability theory on matters
such as discrete vs. continuous distributions, likelihood, and conditional distributions. We provide links on non-obvious
topics and concepts to external sources wherever necessary to bring the audience a vetted and beginner friendly source
to start learning on the more complicated topics. Follow along for a high-level overview into the reason that protein
language models have been so successful across a broad range of tasks.

2. What is a language model?

Under the hood, all language models are nothing more than probability distributions over tokens, or discrete sub-
sequences. In natural language, a very intuitive set of tokens are the words of a language, or perhaps even the
characters. Both have their own pros and cons. For simplicity, let's work with words as tokens here, though this changes
for proteins. Since the learned distribution is over discrete units (words), this distribution is a categorical distribution, not
a continuous one. To make this more concrete, take for example a common language model that you have likely
interacted with many times in your life: text auto-complete. Text auto-complete is a conditional language model that
takes the previous words you have written and then computes the conditional probability over all the words in its
vocabulary and returns the highest probability words based on the context. If you'd like a very intuitive and fine-grained
explanation for both the form and function of language models, the 3Blue1Brown walk-through is a great resource that
breaks down the basics of the architecture, the flow of information, and the process of training a specific LLM (GPT). In
this section we skip over the architecture of the language models and instead leave them as a black-box, focusing more
on the how language models learn from sequences to better motivate their use in the protein domain.

A simple way to visualize what a language model is doing in the background is to think of the language model as
updating and indexing a huge square matrix of transition probabilities of size

, where

is the vocabulary size of the model. Here vocabulary size refers to the number of unique words or sub-words that make
up the state space of the categorical distribution. So a model that only knows the words ['a', 'boy', 'cute', 'is', 'student',
'the' 'walking'] has a vocabulary size of 7. If we start off with an untrained model that is randomly initialized, we can use
a uniform initialization we would get a transition matrix that looks something like this where we introduce a special word
to designate the end of sequence (EOS):

a boy cute is student the walking EOS

a 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

boy 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

cute 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

is 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

student 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

the 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

walking 0.125 0.125 0.125 0.125 0.125 0.125 0.125 0.125

However, if we look at some of the transition probabilities, we can immediately see that the model is not very good. For
example, the probability of the word 'a' coming after 'a' should be close to 0. Same goes for the word 'the' coming after
'a'. It's pretty clear that we need some way of training this model so that we can get some realistic transition
probabilities.

3. Methods for learning language

3.1 Causal Modeling

The first language models were trained on the principle of causal language modeling, where the model is tasked with
next word prediction during each training step.

After enough rounds of this training protocol the model learns a much more plausible distribution over the words -
something that looks like the following:

a boy cute is student the walking EOS

a 0.0 0.5 0.1 0.05 0.25 0.05 0.05 0.0

boy 0.15 0.0 0.1 0.4 0.05 0.15 .05 0.1

cute 0.05 0.2 0.0 0.1 0.25 0.1 0.0 0.3

is 0.2 0.0 0.3 0.0 0.0 0.2 0.3 0.0

student 0.15 0.05 0.1 0.5 0.0 0.05 .05 0.1

the 0.0 0.5 .2 0.0 0.25 0.0 0.05 0.0

walking 0.1 .0 .05 .2 .05 0.35 0.0 0.3

EOS 0.0 0.0 0.0 0.0 0.0 0.0 0.0 1.0

Here we can see that the model has learned that the words above are not typically repeated twice in a row. It assigns
subject words ['boy', 'student'] after the word 'the' with higher probability than the verbs ['is', 'walking']. If we start at
'the' and sample the most likely words at each transition we can generate the following sentence as a path through the
model: 'the' -> 'boy' -> 'is' -> 'walking' -> 'EOS'. This mode of sampling a word at every time step and then conditioning
on the previously sampled words is known as auto-regressive generation.

3.2 The Power of Neural Networks

A key point here that motivates the use of increasingly complicated neural networks for language modeling tasks is that
with our illustrative example, we have the transition probability matrix and each step we sample from it like a markov
chain. However, there are longer range dependencies in language that are not captured simply by conditioning on the
previous word. So why not construct matrices that map transition probabilities between pairs of words or triples, or even
more? Beyond issues of computational feasibility, this model would require that all possible n-grams would have been
seen at least once during training, which greatly limits the models learning and usability. Neural networks have
emerged as a great way of using large contexts and generating a neural representation of the sequence before indexing
a loose transition matrix that maps between the neural representation and all the words in the vocabulary. For this
reason, we often see in the language model space the distribution over the vocabulary from the last layer of a neural
network as a one-dimensional probability distribution rather than a probability matrix. Keeping this in mind, we can see
how these language models accommodate another method of learning language that draws from the context before
AND after a word.

3.3 Masked Language Modeling

Causal language modeling has a key drawback in that sometimes the necessary context to make sense of a word in a
sentence comes after the word and not before. Masked language modeling is like causal modeling, but makes use of the
fact that context may come before and after the word of interest.

This approach is what underlies the powerful BERT [3] language model, where they used a masking rate of about 15% of
the words. Amazingly, this approach has been tried on sequences other than language and has been shown to be a
robust model for learning the syntax and semantics of sequential data of various modalities including time series data,
videos, and yes even proteins!

4. How do Protein Language Models (pLMs) work?

Inspired by the success of large language models (LLMs) in a broad variety of natural language tasks, protein language
models represent a powerful new approach in understanding the syntax and semantics of protein sequences [6]. These
models are trained on using the masked language modeling objective to mask out portions of the sequence and infer
what amino acids belong across billions of protein sequences, learning to identify patterns and relationships within the
sequences that are crucial for their structure and function. This step is called pre-training and it imbues the language
model with a general understanding of the structural dependencies within the language, in this case proteins.

An optional second training step known as fine-tuning can be applied on a pre-trained protein language model, to
further train it on a specific task with protein sequence examples annotated with labels. In practice, starting from the
pretrained weights has shown to have better performance than starting from randomly initialized weights as the model
simply learns how to use strong representations of the inputs (learned during pretraining) instead of jointly learning the
representation AND how to use it. PLMs finetuned on the mappings between specific protein families or functional
classes can significantly enhance predictive power compared to non-pretrained models, and can be applied in a number
of different use cases, such as predicting binding sites or the effects of mutations.

One of the most compelling benefits of PLMs is their ability to capture coevolutionary relationships within and across
protein sequences [7]. In the same way that words in a sentence co-occur to convey coherent meaning, amino acid
residues in a protein sequence co-evolve to maintain the protein's structural integrity and functionality. PLMs capture
these coevolutionary patterns, allowing for the prediction of how changes in one part of a protein may affect other parts.
Thus, from a design perspective, the directed evolution task is an area where PLMs offer substantial advantages. In a
directed evolution experiment, a naturally occurring protein can be mutated according to any arbitrary heuristic and is
then checked if a desired function has improved. Since PLMs capture intra-sequence conditional distributions, this
process can be vastly streamlined by masking portions of the protein we wish to 'mutate' and sampling from the
distribution of what amino acids are strong candidates to occur given the rest of the sequence. PLMs thus have the
potential to significantly reduce experimental burden by identify promising candidates a higher hit rate.

4.1 Reconciling Sequence and Structure

Some protein language models combine in their training input amino acid sequence data with structural data, such as
3D coordinates of atoms in the protein. The goal is to explicitly incorporate structural information information, aiming to
enhance the representation and ultimately prediction of unseen protein structure and functions. This is in contrast to
sequence-only models that implicitly model structure which is more closely conserved across proteins via homology.

Models like ESM-1b [4] and ESM-2 [8] are examples of sequence-only pLMs that do not explicitly incorporate 3D
structural information. These sequence-based pLMs have demonstrated impressive performance on a variety of protein
function prediction tasks by learning patterns from large protein sequence datasets. However, the lack of structural
information can limit the generalization capabilities of sequence-only PLMs. This is true especially for applications
heavily dependent on protein structure such as contact prediction. Moreoever, the inclusion of structural information
helps overcome the distributional biases that exist in the training datasets of sequences.

Structure-aware pLMs like S-PLM[9] and ESM-Fold [8] are trained on both sequence and structural information, and in
turn generate protein representations that encode both sequence and structural information. These models use various
methods such as multi-view contrastive learning to align the sequence and structure representations in a shared latent
space (S-PLM). The structural awareness enables them to achieve comparable or superior performance to specialized
structure-based methods or sequence-based pLMs, particularly for applications that heavily rely on protein structure.

Interestingly, the recently released ESM-3 [10] pLM reasons over sequence, structure, and function, meaning that for
each protein, its sequence, structure, and function are extracted, tokenized, and partially masked during pre-training.

The framework of S-PLM and lightweight tuning strategies for downstream supervised learning. a, The framework of S-
PLM: During pretraining, the model inputs both the amino acid sequences and contact maps derived from protein
structures simultaneously. After pretraining, the ESM-Adapter that generates the AA-level embeddings before the
projector layer is used for downstream tasks. The entire ESM-Adapter model can be fully frozen or learnable through
lightweight tuning. b, Architecture of the ESM-Adapter. c, Adapter tunning for supervised downstream tasks. d, LoRA
tuning for supervised downstream tasks is implemented. Adapted from [9].

5. MSA-aware vs non-MSA-aware protein language models

Multiple Sequence Alignment (MSA) is a method used to align three or more biological sequences (protein or nucleic
acid) to identify regions of similarity that may indicate functional, structural, or evolutionary relationships. MSAs are a
cornerstone in bioinformatics for tasks such as phylogenetic analysis, structure prediction, and function annotation.

In the context of pLMs, MSA provides evolutionary context to the representations of protein sequences. PLMs can be
MSA-aware and non-MSA-aware:

MSA-aware models:

MSA-aware models, such as the MSA Transformer [11], Evoformer (used in AlphaFold) [12] and ESM-MSA [11], are
trained on datasets that include MSAs as input to incorporate evolutionary information and relationships between
sequences to learn richer representations. They align multiple homologous sequences to capture conserved and
variable regions. The rationale is that conserved regions often indicate functionally or structurally important parts of the
protein, while variable regions can provide insights into evolutionary divergence and adaptation.

MSA-aware models can provide deeper insights into protein function and structure due to the evolutionary context.
However, they are computationally intensive and require high-quality MSAs, which may not be available for all protein
families.
Non-MSA-aware models:

Non-MSA-aware models, such as ESMFold (ESM-2)[8], ProtBERT [6] and TAPE, treat each protein sequence
independently and do not explicitly incorporate evolutionary information from MSAs. They are trained on large datasets
of individual protein sequences, learning patterns and representations directly from the sequence data.

While they can generalize well to diverse sequences and are computationally efficient, they may miss out on the
evolutionary context that can be crucial for certain tasks.

"Multiple Sequence Alignment". BioRender.

Benefits and challenges of MSA-aware models:

Evolutionary insight: MSAs provide evolutionary information, highlighting conserved residues that are often critical
for protein function and structure.
Improved predictions: By incorporating evolutionary context, MSA-aware models can improve performance on tasks
such as secondary structure prediction, contact prediction, and function annotation.
Functional and structural understanding: MSAs help in identifying functionally important regions and understanding
the structural constraints of proteins.
Computational complexity: Generating and processing MSAs is computationally expensive and time-consuming.
Data availability: High-quality MSAs are not available for all protein families, especially those with few known
homologs.
Model complexity: MSA-aware models are more complex and require sophisticated architectures to effectively utilize
the evolutionary information.

Other considerations:

The performance benchmark of both MSA-aware and not MSA-aware for predicting the 3D structure of proteins, as
well as their function and other properties is currently an active topic of research.
Interestingly, MSA-free models have reported ability to efficiently generate sufficiently accurate MSAs that can be
used as input for the MSA-aware models.

Without further ado, lets explore some of the properties of protein language models in the wild!

6. Evolutionary statistics of Hemoglobin and its ProtBERT

learned representation

Image Source: Adapted from "Représentation simplifiée de l'hémoglobine et de l'hème". Wikimedia Commons.

Hemoglobin is the protein responsible for transporting oxygen from the lungs to all the cells of our body via red blood
cells. Hemoglobin is a great protein to interrogate the behaviors of protein language models as it is highly conserved in
certain regions across species, and also slightly variable in other places. What would we expect the distribution over
amino acids to look like if we mask out a highly conserved region? What about a highly diverse region? Let's find out.
Hemoglobin Sequence Homology across closely related mammals (from [13]):

hemoglobin_beta = {
'human':
"MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLA
'chimpanzee':
"MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTORFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLVCVLA
'camel':
"MVHLSGDEKNAVHGLWSKVKVDEVGGEALGRLLVVYPWTRRFFESFGDLSTADAVMNNPKVKAHGSKVLNSFGDGLNHLDNLKGTYAKLSELHCDKLHVDPENFRLLGNVLVVVLA
'rabbit':
"MVHLSSEEKSAVTALWGKVNVEEVGGEALGRLLVVYPWTQRFFESFGDLSSANAVMNNPKVKAHGKKVLAAFSEGLSHLDNLKGTFAKLSELHCDKLHVDPENFRLLGNVLVIVLS
'pig':
"MVHLSAEEKEAVLGLWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSNADAVMGNPKVKAHGKKVLQSFSDGLKHLDNLKGTFAKLSELHCDQLHVDPENFRLLGNVIVVVLA
'horse':
"*VQLSGEEKAAVLALWDKVNEEEVGGEALGRLLVVYPWTQRFFDSFGDLSNPGAVMGNPKVKAHGKKVLHSFGEGVHHLDNLKGTFAALSELHCDKLHVDPENFRLLGNVLVVVLA
'bovine':
"M**LTAEEKAAVTAFWGKVKVDEVGGEALGRLLVVYPWTQRFFESFGDLSTADAVMNNPKVKAHGKKVLDSFSNGMKHLDDLKGTFAALSELHCDKLHVDPENFKLLGNVLVVVLA
'sheep':
"M**LTAEEKAAVTGFWGKVKVDEVGAEALGRLLVVYPWTQRFFEHFGDLSNADAVMNNPKVKAHGKKVLDSFSNGMKHLDDLKGTFAQLSELHCDKLHVDPENFRLLGNVLVVVLA
}

As we can see there is a great degree of overlap between the hemoglobin

subunits across the animal kingdom. The part of the hemoglobin sequence that is essential to the function of carrying
oxygen is the part that binds to the heme group. This is handled by a single amino acid, namely the Histidine (H) near
position 92 on the beta chain, in the middle of the underlined subsequences above. Unsurprsingly, given its functional
importance, the amino acid (H) at position is unchanged across all species. Can a language model recapitulate this?

ProtBERT learned representation of Hemoglobin

ProtBERT [6] is a BERT style protein language model that was trained via masked amino acid modeling on Uniref100
[14], a dataset consisting of 217 million protein sequences, and 88B amino acids. The Uniref database contains
deduplicated protein sequences from UniProt where they are clustered together, and thus deduplicated, given the
threhold of sequence identity between species. Uniref100 takes 100% sequence identity, while Uniref90 does 90% and
Uniref50% has a cutoff of 50%. As such, ProtBERT was trained on the largest of these databases. Lets load up ProtBERT
and see what it looks like.

### Step 1. Download ProtBERT Weights from the HF repo

from transformers import BertForMaskedLM, BertTokenizer, pipeline
tokenizer = BertTokenizer.from_pretrained("Rostlab/prot_bert", do_lower_case=False )
model = BertForMaskedLM.from_pretrained("Rostlab/prot_bert")
model

/usr/local/lib/python3.10/dist-packages/huggingface_hub/utils/_token.py:89: UserWarning:
The secret `HF_TOKEN` does not exist in your Colab secrets.
To authenticate with the Hugging Face Hub, create a token in your settings tab (https://huggingface.co/settings/
tokens), set it as secret in your Google Colab and restart your session.
You will be able to reuse this secret in all of your notebooks.
Please note that authentication is recommended but still optional to access public models or datasets.
warnings.warn(
tokenizer_config.json: 0%| | 0.00/86.0 [00:00<?, ?B/s]
vocab.txt: 0%| | 0.00/81.0 [00:00<?, ?B/s]
special_tokens_map.json: 0%| | 0.00/112 [00:00<?, ?B/s]
/usr/local/lib/python3.10/dist-packages/huggingface_hub/file_download.py:1132: FutureWarning: `resume_download`
is deprecated and will be removed in version 1.0.0. Downloads always resume when possible. If you want to force
a new download, use `force_download=True`.
warnings.warn(
config.json: 0%| | 0.00/361 [00:00<?, ?B/s]
pytorch_model.bin: 0%| | 0.00/1.68G [00:00<?, ?B/s]
Some weights of the model checkpoint at Rostlab/prot_bert were not used when initializing BertForMaskedLM: ['ber
t.pooler.dense.bias', 'bert.pooler.dense.weight', 'cls.seq_relationship.bias', 'cls.seq_relationship.weight']
- This IS expected if you are initializing BertForMaskedLM from the checkpoint of a model trained on another tas
k or with another architecture (e.g. initializing a BertForSequenceClassification model from a BertForPreTrainin
g model).
- This IS NOT expected if you are initializing BertForMaskedLM from the checkpoint of a model that you expect to
be exactly identical (initializing a BertForSequenceClassification model from a BertForSequenceClassification mo
del).
BertForMaskedLM(
(bert): BertModel(
(embeddings): BertEmbeddings(
(word_embeddings): Embedding(30, 1024, padding_idx=0)
(position_embeddings): Embedding(40000, 1024)
(token_type_embeddings): Embedding(2, 1024)
(LayerNorm): LayerNorm((1024,), eps=1e-12, elementwise_affine=True)
(dropout): Dropout(p=0.0, inplace=False)
)
(encoder): BertEncoder(

(layer): ModuleList(
(0-29): 30 x BertLayer(
(attention): BertAttention(
(self): BertSdpaSelfAttention(
(query): Linear(in_features=1024, out_features=1024, bias=True)
(key): Linear(in_features=1024, out_features=1024, bias=True)
(value): Linear(in_features=1024, out_features=1024, bias=True)
(dropout): Dropout(p=0.0, inplace=False)
)
(output): BertSelfOutput(
(dense): Linear(in_features=1024, out_features=1024, bias=True)
(LayerNorm): LayerNorm((1024,), eps=1e-12, elementwise_affine=True)
(dropout): Dropout(p=0.0, inplace=False)
)
)
(intermediate): BertIntermediate(
(dense): Linear(in_features=1024, out_features=4096, bias=True)
(intermediate_act_fn): GELUActivation()
)
(output): BertOutput(
(dense): Linear(in_features=4096, out_features=1024, bias=True)
(LayerNorm): LayerNorm((1024,), eps=1e-12, elementwise_affine=True)
(dropout): Dropout(p=0.0, inplace=False)
)
)
)
)
)
(cls): BertOnlyMLMHead(
(predictions): BertLMPredictionHead(
(transform): BertPredictionHeadTransform(
(dense): Linear(in_features=1024, out_features=1024, bias=True)
(transform_act_fn): GELUActivation()
(LayerNorm): LayerNorm((1024,), eps=1e-12, elementwise_affine=True)
)
(decoder): Linear(in_features=1024, out_features=30, bias=True)
)
)
)

### Step 2. Mask the F8 Histidine of Hemoglobin B Subunit

human_heme = list(hemoglobin_beta['human'])
human_heme[92] = "[MASK]"
masked_heme = ' '.join(human_heme)
print(masked_heme)

M V H L T P E E K S A V T A L W G K V N V D E V G G E A L G R L L V V Y P W T Q R F F E S F G D L S T P D A V M
G N P K V K A H G K K V L G A F S D G L A H L D N L K G T F A T L S E L [MASK] C D K L H V D P E N F R L L G N V
L V C V L A H H F G K E F T P P V Q A A Y Q K V V A G V A N A L A H K Y H

### Step 3. Tokenize the Sequence

tokenized_sequence = tokenizer(masked_heme, return_tensors='pt')
tokenized_sequence
{'input_ids': tensor([[ 2, 21, 8, 22, 5, 15, 16, 9, 9, 12, 10, 6, 8, 15, 6, 5, 24, 7,
12, 8, 17, 8, 14, 9, 8, 7, 7, 9, 6, 5, 7, 13, 5, 5, 8, 8,
20, 16, 24, 15, 18, 13, 19, 19, 9, 10, 19, 7, 14, 5, 10, 15, 16, 14,
6, 8, 21, 7, 17, 16, 12, 8, 12, 6, 22, 7, 12, 12, 8, 5, 7, 6,
19, 10, 14, 7, 5, 6, 22, 5, 14, 17, 5, 12, 7, 15, 19, 6, 15, 5,
10, 9, 5, 4, 23, 14, 12, 5, 22, 8, 14, 16, 9, 17, 19, 13, 5, 5,
7, 17, 8, 5, 8, 23, 8, 5, 6, 22, 22, 19, 7, 12, 9, 19, 15, 16,
16, 8, 18, 6, 6, 20, 18, 12, 8, 8, 6, 7, 8, 6, 17, 6, 5, 6,
22, 12, 20, 22, 3]]), 'token_type_ids': tensor([[0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0
, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0, 0,
0, 0, 0, 0, 0]]), 'attention_mask': tensor([[1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1,
1, 1, 1, 1, 1,
1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1,
1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1,
1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1,
1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1,
1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1, 1,
1, 1, 1, 1, 1]])}

### Step 4. Pass the tokenized sequence through ProtBERT

model_outs = model(**tokenized_sequence)
model_outs

MaskedLMOutput(loss=None, logits=tensor([[[-18.5725, -18.4833, -18.4627, ..., -18.6075, -18.6886, -18.5834],

[-19.9242, -21.0844, -20.1253, ..., -18.1157, -19.4804, -19.9197],
[-17.1929, -18.2174, -17.2419, ..., -18.0640, -17.8393, -17.1908],
...,
[-19.3707, -19.7466, -19.2460, ..., -21.4760, -20.1202, -22.1149],
[-19.6403, -20.1926, -18.5551, ..., -17.4572, -18.9988, -21.0471],
[-18.8277, -19.8305, -18.5255, ..., -16.8518, -18.2768, -18.0429]]],
grad_fn=<ViewBackward0>), hidden_states=None, attentions=None)

### Step 5. Transform the Logits

import torch.nn.functional as F
logits = model_outs.logits.squeeze()[1:-1] # Ignore SOS and EOS special tokens
print(logits.shape)
softmaxed = F.softmax(logits, dim=1).detach().numpy() # Softmax to normalize the logits to sum to 1

torch.Size([147, 30])

### Step 6. Decode the Logits Using Greedy Decoding (Max Probability at Each Timestep)
decoded_outputs = tokenizer.batch_decode(softmaxed.argmax(axis=1))
decoded_sequence = ''.join(decoded_outputs)
print(decoded_sequence)
print(f'The filled-in masked sequence is: {decoded_sequence[92]}')

MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLKHLDNLKGTFATLSELHCDKLHVDPENFRLLGNVLV
CVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH
The filled-in masked sequence is: H

Sanity Check: Whew, looks like the pLM ProtBERT was able to recapitulate the correct amino acid at that position. But
how confident was the model? Let's visualize the distribution at that position and see what other amino acids the model
was choosing between.

### Step 7. Visualize the Token Distribution at the F8 Histidine

import matplotlib.pyplot as plt

plt.bar(tokenizer.get_vocab().keys(), softmaxed[92])
plt.ylabel('Normalized Probability')
plt.xlabel('Model Vocabulary')
plt.title('Target Distribution at the F8 Histidine')
plt.xticks(rotation='vertical')
plt.show()
### [EXTRA] Step 8. Visualize the Logits Map Across All Positions
import seaborn as sns

plt.figure(figsize=(10,16))
sns.heatmap(softmaxed, xticklabels=tokenizer.get_vocab())
plt.show()
### [EXTRA] Step 9. Look at a Low Confidence Region

plt.bar(tokenizer.get_vocab().keys(), softmaxed[87])
plt.ylabel('Normalized Probability')
plt.xlabel('Model Vocabulary')
plt.title('Target Distribution at Position 87')
plt.xticks(rotation='vertical')
plt.show()

for animal in hemoglobin_beta:

print(f'{animal} has residue {hemoglobin_beta[animal][87]} at position 87')

human has residue T at position 87

chimpanzee has residue T at position 87
camel has residue K at position 87
rabbit has residue K at position 87
pig has residue K at position 87
horse has residue A at position 87
bovine has residue A at position 87
sheep has residue Q at position 87

As we can see from the above, at the positions where is lower confidence, there tends to be an increase in diversity
among the different species. This aligns well with out understanding of what the categorical distribution would look like
if we took calculated the probabilities of each of the amino acids using all the homologous proteins in the protein
universe.

7. Concluding Thougts
We hope you liked this Tutorial 0 on protein language models. While subsequent tutorials will cover more of the
architecture of the protein language models, the learned representations, and the applications of this remarkable class
of methods, we hope that this work helps ground you in when going through all the details. Analyzing the input/outputs
of pLMs using this lens has helped me understand why performance disparities for certain examples and understand the
failure modes that these models can encounter. For a quick reference, some of their strengths and limitations as they
fall within the scope of the tutorial are summarized below:

7.1 Strengths
pLMs learn co-evolutionary statistics of residues across diverse protein families [7].
They capture information on structure and function from protein sequence alone (most available and accurate
modality by far).

7.2 Limitations
pLMs demonstrate poorer performance on learning the sequence distributions of highly mutated/variable protein
sequences. They bias towards germline sequences [15]

Current pLMs are biased towards the sequences derived from canonically studied model organisms [16]

Citing this Tutorial

If you found this tutorial useful, please consider citing it as:

@manual{Bioinformatics,
title={Protein Language Models (Intuition): A First Look at Modeling Syntax and Semantics of
the Known Protein Universe},
organization={DeepChem},
author={Karthikeyan, Dhuvarakesh and Menezes, Aaron and de Lope, Elisa Gomez},
howpublished =
{\\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/ProteinLM_Tutorial0.ipynb}},

year={2024},
},

References
[1] Mikolov, T., Chen, K., Corrado, G., & Dean, J. (2013). Efficient Estimation of Word Representations in Vector Space.
arXiv [Cs.CL]. Retrieved from http://arxiv.org/abs/1301.3781

[2] Jeffrey Pennington, Richard Socher, and Christopher Manning. 2014. GloVe: Global Vectors for Word Representation.
In Proceedings of the 2014 Conference on Empirical Methods in Natural Language Processing (EMNLP), pages 1532–
1543, Doha, Qatar. Association for Computational Linguistics.

[3] Jacob Devlin, Ming-Wei Chang, Kenton Lee, & Kristina Toutanova. (2019). BERT: Pre-training of Deep Bidirectional
Transformers for Language Understanding.

[4] Rao, R., Meier, J., Sercu, T., Ovchinnikov, S., & Rives, A. (2020). Transformer protein language models are
unsupervised structure learners. bioRxiv. doi:10.1101/2020.12.15.422761

[5] Ibtehaz, N., Kagaya, Y., & Kihara, D. (2023). Domain-PFP: Protein Function Prediction Using Function-Aware Domain
Embedding Representations. bioRxiv. doi:10.1101/2023.08.23.554486

[6] Ahmed Elnaggar, Michael Heinzinger, Christian Dallago, Ghalia Rihawi, Yu Wang, Llion Jones, Tom Gibbs, Tamas
Feher, Christoph Angerer, Martin Steinegger, Debsindhu Bhowmik, & Burkhard Rost. (2021). ProtTrans: Towards
Cracking the Language of Life's Code Through Self-Supervised Deep Learning and High Performance Computing.

[7] Zhidian Zhang, Hannah K. Wayment-Steele, Garyk Brixi, Haobo Wang, Matteo Dal Peraro, Dorothee Kern, Sergey
Ovchinnikov bioRxiv 2024.01.30.577970; doi: https://doi.org/10.1101/2024.01.30.577970

[8] Zeming Lin, Halil Akin, Roshan Rao, Brian Hie, Zhongkai Zhu, Wenting Lu, Nikita Smetanin, Robert Verkuil, Ori Kabeli,
Yaniv Shmueli, Allan dos Santos Costa, Maryam Fazel-Zarandi, Tom Sercu, Salvatore Candido, Alexander Rives bioRxiv
2022.07.20.500902; doi: https://doi.org/10.1101/2022.07.20.500902

[9] Wang D, Pourmirzaei M, Abbas UL, Zeng S, Manshour N, Esmaili F, Poudel B, Jiang Y, Shao Q, Chen J, Xu D. S-PLM:
Structure-aware Protein Language Model via Contrastive Learning between Sequence and Structure. bioRxiv [Preprint].
2024 May 13:2023.08.06.552203. doi: 10.1101/2023.08.06.552203. PMID: 37609352; PMCID: PMC10441326.

[10] Thomas Hayes, Roshan Rao, Halil Akin, Nicholas J. Sofroniew, Deniz Oktay, Zeming Lin, Robert Verkuil, Vincent Q.
Tran, Jonathan Deaton, Marius Wiggert, Rohil Badkundri, Irhum Shafkat, Jun Gong, Alexander Derry, Raul S. Molina, Neil
Thomas, Yousuf Khan, Chetan Mishra, Carolyn Kim, Liam J. Bartie, Matthew Nemeth, Patrick D. Hsu, Tom Sercu,
Salvatore Candido, Alexander Rives bioRxiv 2024.07.01.600583; doi: https://doi.org/10.1101/2024.07.01.600583

[11] Roshan M Rao, Jason Liu, Robert Verkuil, Joshua Meier, John Canny, Pieter Abbeel, Tom Sercu, Alexander Rives
Proceedings of the 38th International Conference on Machine Learning, PMLR 139:8844-8856, 2021.

[12] Jumper, J., Evans, R., Pritzel, A. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–
589 (2021). https://doi.org/10.1038/s41586-021-03819-2

[13] Ali, A., Baby, B., Soman, S.S. et al. Molecular insights into the interaction of hemorphin and its targets. Sci Rep 9,
14747 (2019). https://doi.org/10.1038/s41598-019-50619-w

[15] Shaw, A., Spinner, H., Shin, J., Gurev, S., Rollins, N., & Marks, D. (2023). Removing bias in sequence models of
protein fitness. bioRxiv. doi:10.1101/2023.09.28.560044

[16] Ding, F., & Steinhardt, J. (2024). Protein language models are biased by unequal sequence sampling across the tree
of life. doi:10.1101/2024.03.07.584001
Congratulations! Time to join the Community!
Congratulations on completing this tutorial notebook! If you enjoyed working through the tutorial, and want to continue
working with DeepChem, we encourage you to finish the rest of the tutorials in this series. You can also help the
DeepChem community in the following ways:

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

How to contribute to this/other tutorials

If you have any feedback on the given tutorial, please feel free to reach out by opening a github issue on this tutorial. If
you'd like to build off this tutorial series, there are a couple of places that would be natural and impactful extensions to
this tutorial:

1. Attention Mechanisms and their Significance to Protein Language Models

2. Zhang et al's Categorical Jacobian analysis of pLMs

Feel free to contribute your own ideas on the matter as well.

Introduction to binding sites
By Elisa Gómez de Lope | Twitter

In this tutorial, you will explore the fundamental concepts and computational methods for studying binding sites to
enhance your understanding and analysis of molecular interactions.

Table of Contents:
Introduction
Basic concepts
Types of binding sites
Computational methods to study binding sites
DeepChem tools
How does a binding pocket look like?
Further Reading

This tutorial is made to run without any GPU support, and can be used in Google colab. If you'd like to open this
notebook in colab, you can use the following link.

Open in Colab

Introduction
Binding sites are specific locations on a molecule where ligands, such as substrates, inhibitors, or other molecules, can
attach through various types of molecular interactions.

Binding sites are crucial for the function of many biological molecules. They are typically located on the surface of
proteins or within their three-dimensional structure. When a ligand binds to a binding site, it can induce a
conformational change in the protein, which can either activate or inhibit the protein's function. This binding process is
essential for numerous biological processes, including enzyme catalysis, signal transduction, and molecular recognition.

For example, in enzymes, the binding site where the substrate binds is often referred to as the active site. In receptors,
the binding site for signaling molecules (such as hormones or neurotransmitters) is critical for transmitting signals inside
the cell.

Understanding binding sites is particularly relevant for the development of new drugs, as it can lead to the development
of more effective and selective drugs from multiple angles:

Target identification: Identifying binding sites on target proteins allows researchers to design molecules that can
specifically interact with these sites, leading to the development of drugs that can modulate the protein's activity.
Drug design: Knowledge of the structure and properties of binding sites enables the design of drugs with high
specificity and affinity, reducing off-target effects and increasing efficacy.
Optimization: Detailed understanding of binding interactions helps improving the binding characteristics of drug
candidates, such as increasing binding affinity and selectivity.

Additionally, knowledge of the structure and properties of binding sites enables the design of drugs with high specificity
and affinity, reducing off-target effects and increasing efficacy.
Myoglobin (blue) with its ligand heme (orange) bound. Based on PDB: 1MBO.

Basic concepts
Here we cover some basic notions to understand the science of binding site identification.

Molecular Interactions
The specific interactions that occur at the binding site can be of various types, including (non-exhaustive list):

Hydrogen Bonding: Weak electrostatic interactions between hydrogen atoms bonded to highly electronegative
atoms (like oxygen, nitrogen, or fluorine) and other electronegative atoms or functional groups. Hydrogen bonding is
important for stabilizing protein-ligand complexes and can be enhanced by halogen bonding.

Halogen Bonding: A type of intermolecular interaction where a halogen atom (like iodine or fluorine) acts as an
acceptor, forming a bond with a hydrogen atom or a multiple bond. Halogen bonding can significantly enhance the
affinity of ligands for binding sites.

Orthogonal Multipolar Interactions: Interactions between backbone carbonyls, amide-containing side chains,
guanidinium groups, and sulphur atoms, which can also enhance binding affinity.

Van der Waals Forces: Weak, non-specific interactions arising from induced electrical interactions between closely
approaching atoms or molecules. They usually provide additional stabilization and contribute to the overall binding
affinity, especially in close-contact regions.

Metal coordination: Interactions between metal ions (e.g., zinc, magnesium) and ligands that have lone pairs of
electrons (e.g., histidine, cysteine, water). These interactions are typically coordinate covalent bonds, where both
electrons in the bond come from the ligand, and are crucial in metalloenzymes and metalloproteins, where metal
ions often play a key role in catalytic activity and structural stability.

Polar Interactions: Interactions between polar functional groups, such as hydrogen bond donors (e.g., backbone NH,
polarized Cα–H, polar side chains, and protein-bound water) and acceptors (e.g., backbone carbonyls, amide-
containing side chains, and guanidinium groups).

Hydrophobic Interactions: Non-polar interactions between lipophilic side chains, which can contribute to the binding
affinity of ligands.

Pi Interactions: Interactions between aromatic rings (Pi-Pi), and aromatic rings with other types of molecules
(Halogen-Pi, Cation-Pi,...). They occur in binding sites with aromatic residues such as phenylalanine, tyrosine, and
tryptophan, and stabilize the binding complex through stacking interactions.
Valiulin, Roman A. "Non-Covalent Molecular Interactions". Cheminfographic, 13 Apr. 2020,
https://cheminfographic.wordpress.com/2020/04/13/non-covalent-molecular-interactions

Ligands
Ligands are molecules that bind to specific sites on proteins or other molecules, facilitating various biological processes.

Ligands can be classified into different types based on their function:

Substrates: Molecules that bind to an enzyme's active site and undergo a chemical reaction.
Inhibitors: Molecules that bind to an enzyme or receptor and block its activity.
Activators: Molecules that bind to an enzyme or receptor and increase its activity.
Cofactors: Non-protein molecules (metal ions, vitamins, or other small molecules) that bind to enzymes to modify
their activity. They can act as activators or inhibitors depending on the specific enzyme and the binding site.
Signaling Lipids: Lipid-based molecules that act as signaling molecules, such as steroid hormones.
Neurotransmitters: Chemical messengers that transmit signals between neurons and their target cells.

Protein Ligand Docking. Adobe Stock #216974924.

The binding of ligands to their target sites is influenced by various physicochemical properties:

Size and Shape: Ligands must be the appropriate size and shape to fit into the binding site.
Charge: Electrostatic interactions, such as ionic bonds, can contribute to ligand binding.
Hydrophobicity: Hydrophobic interactions between non-polar regions of the ligand and the binding site can stabilize
the complex.
Hydrogen Bonding: Hydrogen bonds between the ligand and the binding site can also play a crucial role in binding
affinity.

The specific interactions between a ligand and its binding site, as well as the physicochemical properties of the ligand,
are essential for understanding and predicting ligand-receptor binding events

Binding Affinity and Specificity

Binding affinity is the strength of the binding interaction between a biomolecule (e.g., a protein or DNA) and its ligand or
binding partner (e.g., a drug or inhibitor). It is typically measured and reported by the equilibrium dissociation constant (

), which is used to evaluate and rank the strengths of bimolecular interactions. The smaller the

value, the greater the binding affinity of the ligand for its target. Conversely, the larger the

value, the more weakly the target molecule and ligand are attracted to and bind to one another.

Binding affinity is influenced by non-covalent intermolecular interactions, such as hydrogen bonding, electrostatic
interactions, hydrophobic interactions, and van der Waals forces between the two molecules. The presence of other
molecules can also affect the binding affinity between a ligand and its target.

Binding specificity refers to the selectivity of a ligand for binding to a particular site or target. Highly specific ligands will
bind tightly and selectively to their intended target, while less specific ligands may bind to multiple targets with varying
affinities. It is determined by the complementarity between the ligand and the binding site, including factors such as
size, shape, charge, and hydrophobicity (see section above on ligands). Specific interactions, like hydrogen bonding and
ionic interactions, contribute to the selectivity of the binding.

Binding specificity is crucial in various biological processes, such as enzymatic reactions or drug-target interactions, as it
allows for specific and regulated interactions, which is essential for the proper functioning of biological systems.

Antigen-antibody interactions are particularly highly specific binding sites (often also characterized by high affinity). The specificity of these
interactions is fundamental to ensure precise immune recognition and response. Kyowa Kirin. "Specificity of Antibodies".

In summary, binding affinity measures the strength of the interaction between a ligand and its target, while binding
specificity determines the selectivity of the ligand for a particular binding site or target.

Thermodynamics of Binding
The thermodynamics of binding involves the interplay of enthalpy (

), entropy (

), and Gibbs free energy (

) to describe the binding of ligands to binding sites. These thermodynamic parameters are crucial in understanding the
binding process and the forces involved.
Enthalpy (

) is a measure of the total energy change during a process. In the context of binding, enthalpy represents the
energy change associated with the formation of the ligand-binding site complex. A negative enthalpy change
indicates that the binding process is exothermic, meaning that heat is released during binding. Conversely, a
positive enthalpy change indicates an endothermic process, where heat is absorbed during binding.

Entropy (

) measures the disorder or randomness of a system. In binding, entropy represents the change in disorder
associated with the formation of the ligand-binding site complex. A negative entropy change indicates a decrease in
disorder, which is often associated with the formation of a more ordered complex. Conversely, a positive entropy
change indicates an increase in disorder, which can be seen in the disruption of the binding site or the ligand.

Gibbs free energy (

) is a measure of the energy change during a process that takes into account both enthalpy and entropy. It is
defined as

, where

is the temperature in Kelvin. Gibbs free energy represents the energy available for work during a process. In
binding, a negative Gibbs free energy change indicates that the binding process is spontaneous and favorable, while
a positive Gibbs free energy change indicates that the process is non-spontaneous and less favorable.

image.png

Calculated variation of the Gibbs free energy (G), entropy (S), enthalpy (H), and heat capacity (Cp) of a given reaction plotted as a function
of temperature (T). The solid curves correspond to a pressure of 1 bar; The dashed curve shows variation in ∆G at 8 GPa. Ghiorso, Mark S.,
Yang, Hexiong and Hazen, Robert M. "Thermodynamics of cation ordering in karrooite (MgTi2O5)" American Mineralogist, vol. 84, no. 9,
1999, pp. 1370-1374. https://doi.org/10.2138/am-1999-0914

Binding isotherms are models that describe the relationship between the concentration of ligand and the
occupancy of binding sites. These isotherms are crucial in understanding the binding process and the forces
involved. One example is the Langmuir isotherm, which assumes that the binding site is homogeneous and the
ligand binds to the site with a single binding constant.

Cooperative binding occurs when the binding of one ligand molecule affects the binding of subsequent ligand
molecules. This can lead to non-linear binding isotherms, where the binding of ligands is enhanced or inhibited by
the presence of other ligands. Cooperative binding is often seen in systems where multiple binding sites are
involved or where the binding site is heterogeneous.
Kinetics of Binding
The kinetics of binding involves the study of the rates at which ligands bind to and dissociate from binding sites.

Rate constants for association and dissociation are essential in describing the kinetics of binding. They represent
the rate at which the ligand binds or dissociates to the site, respectively.

Kinetic models are used to describe the binding process. One commonly used kinetic model to describe enzyme
kinetics is the Michaelis-Menten model, which assumes that the enzyme has a single binding site and that the
binding of the substrate is reversible. There are other kinetic models, including the Langmuir adsorption model.

Binding curves for three ligands following the Hill-Langmuir model, each with a

(equilibrium dissociation constant) of 10 µM for its target protein. The blue ligand shows negative cooperativity of binding, meaning that
binding of the first ligand reduces the binding affinity of the remaining site(s) for binding of a second ligand. The red ligand shows positive
cooperativity of binding, meaning that binding of the first ligand increases the binding affinity of the remaining site(s) for binding of a
second ligand. "Hill-Langmuir equation". Open Educational Alberta. https://openeducationalberta.ca/abcofpkpd/chapter/hill-langmuir/.

Types of binding sites

Binding sites can be classified based on various criteria depending on the context. This is a non-exhaustive list of
binding sites categories based on the type of molecule they bind to:

Protein Binding Sites: These are regions on a protein where other molecules can bind. They can be further divided
into:
Active Sites: Regions where enzymes bind substrates and catalyze chemical reactions. Example: The active site
of the enzyme hexokinase binds to glucose and ATP, catalyzing the phosphorylation of glucose.
Allosteric Sites: Regions where ligands bind and alter the protein's activity without being part of the active site.
Example: The binding of 2,3-bisphosphoglycerate (2,3-BPG) to hemoglobin enhances the ability of hemoglobin
to release oxygen where it is most needed.
Regulatory Sites: Regions where ligands bind and regulate protein activity or localization. Example: Binding of a
regulatory protein to a specific site on a receptor can modulate the receptor's activity.
Nucleic Acid Binding Sites: These are regions on DNA or RNA where other molecules can bind. They can be further
divided into:
Transcription Factor Binding Sites: Regions where transcription factors bind to regulate gene expression.
Example: The TATA box is a DNA sequence that transcription factors bind to initiate transcription.
Restriction Sites: Regions where restriction enzymes bind to cleave DNA. Example: The EcoRI restriction enzyme
recognizes and cuts the DNA sequence GAATTC.
Recombination Sites: Regions where site-specific recombinases bind to facilitate genetic recombination.
Example: The loxP sites are recognized by the Cre recombinase enzyme to mediate recombination.
Small Molecule Binding Sites: These are regions on proteins or nucleic acids where small molecules like drugs or
substrates bind. They can be further divided into:
Compound Binding Sites: Regions typically located at the active site of the enzyme where the substrate binds
and undergoes a chemical reaction, usually reversible. Example: The binding site for the drug aspirin on the
enzyme cyclooxygenase (COX) inhibits its activity.
Cofactor Binding Sites: Regions where cofactors can bind, sometimes permanently and covalently attached to
the protein, and can be located at various sites. Example: The binding site for the heme cofactor in hemoglobin,
which is essential for oxygen transport.
Ion and Water Binding Sites: These are regions on proteins or nucleic acids where ions or water molecules bind. The
calcium-binding sites in calmodulin, which are crucial for its role in signal transduction.

Computational methods to study binding sites

Multiple computational methods have been developed in the last decades to study and identify binding sites, offering
insights that complement experimental approaches. These methods enable the prediction of binding affinities, the
identification of potential drug candidates, and the understanding of the dynamic nature of binding interactions. Here
are some key computational approaches used to study binding sites:

Method Description Applications Tools Output

Used extensively in drug

Predicts the preferred
discovery to screen large Binding poses, binding
orientation of a ligand when AutoDock,
Molecular Docking libraries of compounds and affinities, interaction
bound to a protein or nucleic Glide, DOCK
identify potential drug maps
acid binding site.
candidates.

Provides a dynamic view of Used to study the stability Trajectories of atomic

the binding process by of ligand binding, GROMACS, positions, binding free
Molecular Dynamics
simulating the physical conformational changes, AMBER, energies, insights into the
(MD) Simulations
movements of atoms and and the effect of mutations CHARMM flexibility and dynamics of
molecules over time. on binding affinity. binding sites

Combines quantum
Quantum Used to study reaction Detailed electronic
mechanical calculations for
Mechanics/Molecular mechanisms, electronic Gaussian, structure information,
the active site with molecular
Mechanics (QM/MM) properties, and the role of ORCA, Q-Chem reaction pathways,
mechanical calculations for
Methods metal ions in binding sites. energy profiles
the rest of the system.

Predicts the 3D structure of a Useful for studying binding Predicted 3D structures

MODELLER,
protein based on the known sites in proteins for which that can be used for
Homology Modeling SWISS-MODEL,
structure of a homologous no experimental structure docking and MD
Phyre2
protein. is available. simulations

Computationally screens large Widely used in drug Schrodinger's Ranked lists of

libraries of compounds to discovery to prioritize Glide, compounds with
Virtual Screening
identify potential ligands that compounds for AutoDock predicted binding
bind to a target binding site. experimental testing. Vina, GOLD affinities and poses

DeepChem,
Uses machine learning and AI Enhancing the accuracy of
TensorFlow, Predictive models,
techniques to predict binding docking predictions,
Machine Learning PyTorch, binding affinity
affinities, identify binding predicting drug-target
and AI protein predictions, novel ligand
sites, and generate new interactions, and designing
language designs
ligand structures. novel compounds.
models (ESM2)

Computational Used to compare binding

Protein-Ligand MOE,
representations of the modes, identify key Interaction maps,
Interaction Schrödinger's
interactions between a interactions, and cluster similarity scores
Fingerprints (PLIF) Maestro
protein and a ligand. similar binding sites.

Recently, large language models, particularly protein language models (PLMs), have emerged as powerful tools for
predicting protein properties. These models typically use a transformer-based architecture to process protein
sequences, learning relationships between amino acids and protein properties. PLMs can then be fine-tuned for specific
tasks, such as binding site prediction, reducing the need for large, specific training datasets and offering high scalability.

DeepChem tools for studying binding sites

DeepChem in particular has a few tools and capabilities for identifying binding pockets on proteins:

BindingPocketFinder: This is an abstract superclass in DeepChem that provides a template for child classes to
algorithmically locate potential binding pockets on proteins. The idea is to help identify regions of the protein that
may be good interaction sites for ligands or other molecules.
ConvexHullPocketFinder: This is a specific implementation of the BindingPocketFinder class that uses the convex
hull of the protein structure to find potential binding pockets. It takes in a protein structure and returns a list of
binding pockets represented as CoordinateBoxes.
Pose generators: Pose generation is the task of finding a “pose”, that is a geometric configuration of a small
molecule interacting with a protein. A key step in computing the binding free energy of two complexes is to find low
energy “poses”, that is energetically favorable conformations of molecules with respect to each other. This can be
useful for identifying favorable binding modes and orientations (low energy poses) of ligands within a protein's
binding site. Current implementations allow for Autodock Vina and GNINA.
Docking: There is a generic docking implementation that depends on provide pose generation and pose scoring
utilities to perform docking.

There is a tutorial on using machine learning and molecular docking methods to predict the binding energy of a protein-
ligand complex, and another tutorial on using atomic convolutions in particular to model such interactions.

How does a binding site look like?

Let's visualize a binding pocket in greater detail. For this purpose, we need to download the structure of a protein that
contains a binding site. As an illustrative example, we show here a well-known protein-ligand pair: the binding of the
drug Imatinib (Gleevec) to the Abl kinase domain of the BCR-Abl fusion protein, which is commonly associated with
chronic myeloid leukemia (CML). The PDB ID for this complex is '1IEP'.

# setup
!pip install py3Dmol biopython requests
import requests
import py3Dmol
from Bio.PDB import PDBParser, NeighborSearch
from io import StringIO

Requirement already satisfied: py3Dmol in /usr/local/lib/python3.10/dist-packages (2.1.0)

Requirement already satisfied: biopython in /usr/local/lib/python3.10/dist-packages (1.83)
Requirement already satisfied: requests in /usr/local/lib/python3.10/dist-packages (2.31.0)
Requirement already satisfied: numpy in /usr/local/lib/python3.10/dist-packages (from biopython) (1.25.2)
Requirement already satisfied: charset-normalizer<4,>=2 in /usr/local/lib/python3.10/dist-packages (from request
s) (3.3.2)
Requirement already satisfied: idna<4,>=2.5 in /usr/local/lib/python3.10/dist-packages (from requests) (3.7)
Requirement already satisfied: urllib3<3,>=1.21.1 in /usr/local/lib/python3.10/dist-packages (from requests) (2.
0.7)
Requirement already satisfied: certifi>=2017.4.17 in /usr/local/lib/python3.10/dist-packages (from requests) (20
24.6.2)

# Download the protein-ligand complex (PDB file)

pdb_id = "1IEP"
url = f"https://files.rcsb.org/download/{pdb_id}.pdb"
response = requests.get(url)
pdb_content = response.text

Let's see what's inside the pdb file:

# Parse the PDB content to identify chains and ligands

chains = {}
for line in pdb_content.splitlines():
if line.startswith("ATOM") or line.startswith("HETATM"):
chain_id = line[21]
resn = line[17:20].strip()
if chain_id not in chains:
chains[chain_id] = {'residues': set(), 'ligands': set()}
chains[chain_id]['residues'].add(resn)
if line.startswith("HETATM"):
chains[chain_id]['ligands'].add(resn)
chains_info = chains
print("Chains and Ligands Information:")
for chain_id, info in chains_info.items():
print(f"Chain {chain_id}:")
print(f" Residues: {sorted(info['residues'])}")
print(f" Ligands: {sorted(info['ligands'])}")

Chains and Ligands Information:

Chain A:
Residues: ['ALA', 'ARG', 'ASN', 'ASP', 'CL', 'CYS', 'GLN', 'GLU', 'GLY', 'HIS', 'HOH', 'ILE', 'LEU', 'LYS', 'M
ET', 'PHE', 'PRO', 'SER', 'STI', 'THR', 'TRP', 'TYR', 'VAL']
Ligands: ['CL', 'HOH', 'STI']
Chain B:
Residues: ['ALA', 'ARG', 'ASN', 'ASP', 'CL', 'CYS', 'GLN', 'GLU', 'GLY', 'HIS', 'HOH', 'ILE', 'LEU', 'LYS', 'M
ET', 'PHE', 'PRO', 'SER', 'STI', 'THR', 'TRP', 'TYR', 'VAL']
Ligands: ['CL', 'HOH', 'STI']

We have a homodimer of two identical chains and several ligands: CL, HOH, and STI. CL and HOH are common solvents
and ions binding to the protein structure, while STI is the ligand of interest (Imatinib).

For visualization, let's extract the information of chain A and its ligands:

chain_id = "A"
chain_lines = []
for line in pdb_content.splitlines():
if line.startswith("HETATM") or line.startswith("ATOM"):
if line[21] == chain_id:
chain_lines.append(line)
elif line.startswith("TER"):
if chain_lines and chain_lines[-1][21] == chain_id:
chain_lines.append(line)
chain_A = "\n".join(chain_lines)

view = py3Dmol.view()

# Add the extracted chain model

view.addModel(chain_A, "pdb")

# Set the styles

view.setStyle({'cartoon': {'color': 'darkgreen'}})
for ligand in chains_info[chain_id]['ligands']:
view.addStyle({'chain': 'A', 'resn': ligand}, {'stick': {'colorscheme': 'yellowCarbon'}})
view.zoomTo()

view.show()

Now let's highlight the binding pocket in the protein ribbon. For this purpose we need to parse the PDB content again to
identify residues belonging to chain A and STI ligand:

parser = PDBParser()
structure = parser.get_structure('protein', StringIO(pdb_content))

# Extract residues of chain A and the ligand STI

str_chain_A = structure[0][chain_id]
ligand = None
ligand_resname = "STI"
for residue in structure.get_residues():
if residue.id[0] != ' ' and residue.resname == ligand_resname:
ligand = residue
break
if ligand is None:
raise ValueError("Ligand STi not found in the PDB content")

chain_A_atoms = [atom for atom in str_chain_A.get_atoms()]

ligand_atoms = [atom for atom in ligand.get_atoms()]

/usr/local/lib/python3.10/dist-packages/Bio/PDB/StructureBuilder.py:89: PDBConstructionWarning: WARNING: Chain A

is discontinuous at line 5038.
warnings.warn(
/usr/local/lib/python3.10/dist-packages/Bio/PDB/StructureBuilder.py:89: PDBConstructionWarning: WARNING: Chain B
is discontinuous at line 5079.
warnings.warn(
/usr/local/lib/python3.10/dist-packages/Bio/PDB/StructureBuilder.py:89: PDBConstructionWarning: WARNING: Chain A
is discontinuous at line 5118.
warnings.warn(
/usr/local/lib/python3.10/dist-packages/Bio/PDB/StructureBuilder.py:89: PDBConstructionWarning: WARNING: Chain B
is discontinuous at line 5217.
warnings.warn(
Now we can find the residues in chain A within a certain distance from the ligand. Here we set this distance to 5Å.

binding_residues = set()
distance_threshold = 5.0
ns = NeighborSearch(chain_A_atoms)

for ligand_atom in ligand_atoms:

close_atoms = ns.search(ligand_atom.coord, distance_threshold)
for atom in close_atoms:
binding_residues.add(atom.get_parent().id[1])

And let's see the visualization, now with the binding pocket:

# Create a py3Dmol view

view = py3Dmol.view()

# Add the chain model

view.addModel(chain_A, "pdb")

# Set the style for the protein

view.setStyle({'cartoon': {'color': 'darkgreen'}})

# Color the binding pocket residues

for resi in binding_residues:
view.addStyle({'chain': chain_id, 'resi': str(resi)}, {'cartoon': {'colorscheme': 'greenCarbon'}})

# Color the ligand

view.addStyle({'chain': chain_id, 'resn': ligand_resname}, {'stick': {'colorscheme': 'yellowCarbon'}})

# Zoom to the view

view.zoomTo()

# Show the view

view.show()

Further Reading
For further reading on computational methods for binding sites and protein language models here are a couple of great
resources:

Exploring the computational methods for protein-ligand binding site prediction -Getting started with protein
language models

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Citing this tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Bioinformatics,
title={Introduction to Binding Sites},
organization={DeepChem},
author={Gómez de Lope, Elisa},
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Introduction_to_Binding_Sites.i

year={2024},
}
Tutorial Part 13: Modeling Protein-Ligand Interactions
By Nathan C. Frey | Twitter and Bharath Ramsundar | Twitter

As you work through the tutorial, you'll trace an arc including

1. Loading a protein-ligand complex dataset (PDBbind)

2. Performing programmatic molecular docking
3. Featurizing protein-ligand complexes with interaction fingerprints
4. Fitting a random forest model and predicting binding affinities

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!pip install -q condacolab

import condacolab
condacolab.install()

!conda install -c conda-forge openmm

Collecting package metadata (current_repodata.json): - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \

# All requested packages already installed.

!pip install deepchem

!conda install -c conda-forge pdbfixer

Collecting package metadata (current_repodata.json): - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \

# All requested packages already installed.

!conda install -c conda-forge vina

Collecting package metadata (current_repodata.json): - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \

| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \
| / - \ | / - \ | / - \ | / - \ | / - \ done
Solving environment: / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / - \ | / done

# All requested packages already installed.

Protein-ligand complex data

!pip install -q mdtraj nglview

# !jupyter-nbextension enable nglview --py --sys-prefix # for jupyter notebook
# !jupyter labextension install nglview-js-widgets # for jupyter lab

import os
import numpy as np
import pandas as pd

import tempfile

from rdkit import Chem

from rdkit.Chem import AllChem
import deepchem as dc

from deepchem.utils import download_url, load_from_disk

raw_dataset = load_from_disk(dataset_file)
raw_dataset = raw_dataset[['pdb_id', 'smiles', 'label']]

Let's see what raw_dataset looks like:

raw_dataset.head(2)

pdb_id smiles label

0 2d3u CC1CCCCC1S(O)(O)NC1CC(C2CCC(CN)CC2)SC1C(O)O 6.92

1 3cyx CC(C)(C)NC(O)C1CC2CCCCC2C[NH+]1CC(O)C(CC1CCCCC... 8.00

Fixing PDB files

from openmm.app import PDBFile

from pdbfixer import PDBFixer

from deepchem.utils.vina_utils import prepare_inputs

# consider one protein-ligand complex for visualization

pdbid = raw_dataset['pdb_id'].iloc[1]
ligand = raw_dataset['smiles'].iloc[1]

%%time
fixer = PDBFixer(pdbid=pdbid)
PDBFile.writeFile(fixer.topology, fixer.positions, open('%s.pdb' % (pdbid), 'w'))

p, m = None, None
# fix protein, optimize ligand geometry, and sanitize molecules
try:
p, m = prepare_inputs('%s.pdb' % (pdbid), ligand)
except:
print('%s failed PDB fixing' % (pdbid))

if p and m: # protein and molecule are readable by RDKit

print(pdbid, p.GetNumAtoms())
Chem.rdmolfiles.MolToPDBFile(p, '%s.pdb' % (pdbid))
Chem.rdmolfiles.MolToPDBFile(m, 'ligand_%s.pdb' % (pdbid))

Visualization
If you're outside of Colab, you can expand these cells and use MDTraj and nglview to visualize proteins and ligands.

import mdtraj as md
import nglview

from IPython.display import display, Image

Let's take a look at the first protein ligand pair in our dataset:

v = nglview.show_mdtraj(ligand_mdtraj)

display(v) # interactive view outside Colab

NGLWidget()

Now that we have an idea of what the ligand looks like, let's take a look at our protein:

view = nglview.show_mdtraj(protein_mdtraj)
display(view) # interactive view outside Colab

NGLWidget()

finder = dc.dock.binding_pocket.ConvexHullPocketFinder()
pockets = finder.find_pockets('3cyx.pdb')
len(pockets) # number of identified pockets

Pose generation is quite complex. Luckily, using DeepChem's pose generator will install the AutoDock Vina engine under
the hood, allowing us to get up and running generating poses quickly.

vpg = dc.dock.pose_generation.VinaPoseGenerator()

!mkdir -p vina_test

%%time
complexes, scores = vpg.generate_poses(molecular_complex=('3cyx.pdb', 'ligand_3cyx.pdb'), # protein-ligand files for
out_dir='vina_test',
generate_scores=True
)

We used the default value for num_modes when generating poses, so Vina will return the 9 lowest energy poses it found
in units of kcal/mol .

scores

[-9.484, -9.405, -9.195, -9.151, -8.9, -8.696, -8.687, -8.633, -8.557]

Can we view the complex with both protein and ligand? Yes, but we'll need to combine the molecules into a single RDkit
molecule.

complex_mol = Chem.CombineMols(complexes[0][0], complexes[0][1])

Let's now visualize our complex. We can see that the ligand slots into a pocket of the protein.

v = nglview.show_rdkit(complex_mol)
display(v)

NGLWidget()

Now that we understand each piece of the process, we can put it all together using DeepChem's Docker class. Docker
creates a generator that yields tuples of posed complexes and docking scores.

docker = dc.dock.docking.Docker(pose_generator=vpg)
posed_complex, score = next(docker.dock(molecular_complex=('3cyx.pdb', 'ligand_3cyx.pdb'),
use_pose_generator_scores=True))

Modeling Binding Affinity

pdbids = raw_dataset['pdb_id'].values
ligand_smiles = raw_dataset['smiles'].values

if p and m: # protein and molecule are readable by RDKit

Chem.rdmolfiles.MolToPDBFile(p, '%s.pdb' % (pdbid))
Chem.rdmolfiles.MolToPDBFile(m, 'ligand_%s.pdb' % (pdbid))

proteins = [f for f in os.listdir('.') if len(f) == 8 and f.endswith('.pdb')]

ligands = [f for f in os.listdir('.') if f.startswith('ligand') and f.endswith('.pdb')]

# Handle failed sanitizations

failures = set([f[:-4] for f in proteins]) - set([f[7:-4] for f in ligands])
for pdbid in failures:
proteins.remove(pdbid + '.pdb')
len(proteins), len(ligands)

(190, 190)

pdbids = [f[:-4] for f in proteins]

small_dataset = raw_dataset[raw_dataset['pdb_id'].isin(pdbids)]
labels = small_dataset.label

fp_featurizer = dc.feat.CircularFingerprint(size=2048)

features = fp_featurizer.featurize([Chem.MolFromPDBFile(l) for l in ligands])

dataset = dc.data.NumpyDataset(X=features, y=labels, ids=pdbids)

train_dataset, test_dataset = dc.splits.RandomSplitter().train_test_split(dataset, seed=42)

# # Uncomment to featurize all of PDBBind's "refined" set

Now, we're ready to do some learning!

from sklearn.ensemble import RandomForestRegressor

from deepchem.utils.evaluate import Evaluator

import pandas as pd

seed = 42 # Set a random seed to get stable results

sklearn_model = RandomForestRegressor(n_estimators=100, max_features='sqrt')
sklearn_model.random_state = seed
model = dc.models.SklearnModel(sklearn_model)
model.fit(train_dataset)

Note that the R 2

# use Pearson correlation so metrics are > 0

metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)

evaluator = Evaluator(model, train_dataset, [])

train_r2score = evaluator.compute_model_performance([metric])
print("RF Train set R^2 %f" % (train_r2score["pearson_r2_score"]))

evaluator = Evaluator(model, test_dataset, [])

test_r2score = evaluator.compute_model_performance([metric])
print("RF Test set R^2 %f" % (test_r2score["pearson_r2_score"]))

RF Train set R^2 0.888697

RF Test set R^2 0.007797

We're using a very small dataset and an overly simplistic representation, so it's no surprise that the test set
performance is quite bad.

# Compare predicted and true values

list(zip(model.predict(train_dataset), train_dataset.y))[:5]

[(6.862549999999994, 7.4),
(6.616400000000008, 6.85),
(4.852004999999995, 3.4),
(6.43060000000001, 6.72),
(8.66322999999999, 11.06)]

list(zip(model.predict(test_dataset), test_dataset.y))[:5]
[(5.960549999999999, 4.21),
(6.051305714285715, 8.7),
(5.799900000000003, 6.39),
(6.433881666666665, 4.94),
(6.7465399999999995, 9.21)]

The protein-ligand complex view.

fp_featurizer = dc.feat.ContactCircularFingerprint(size=2048)

features = fp_featurizer.featurize(zip(ligands, proteins))

dataset = dc.data.NumpyDataset(X=features, y=labels, ids=pdbids)
train_dataset, test_dataset = dc.splits.RandomSplitter().train_test_split(dataset, seed=42)

[15:21:40] Explicit valence for atom # 3 C, 5, is greater than permitted

Let's now train a simple random forest model on this dataset.

seed = 42 # Set a random seed to get stable results

sklearn_model = RandomForestRegressor(n_estimators=100, max_features='sqrt')
sklearn_model.random_state = seed
model = dc.models.SklearnModel(sklearn_model)
model.fit(train_dataset)

Let's see what our accuracies looks like!

metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)

evaluator = Evaluator(model, train_dataset, [])

train_r2score = evaluator.compute_model_performance([metric])
print("RF Train set R^2 %f" % (train_r2score["pearson_r2_score"]))

evaluator = Evaluator(model, test_dataset, [])

test_r2score = evaluator.compute_model_performance([metric])
print("RF Test set R^2 %f" % (test_r2score["pearson_r2_score"]))

RF Train set R^2 0.536155

RF Test set R^2 0.000014

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This DeepChem tutorial introduces the Atomic Convolutional Neural Network. We'll see the structure of the
AtomicConvModel and write a simple program to run Atomic Convolutions.

Distance Matrix
The distance matrix

is constructed from the Cartesian atomic coordinates

. It calculates distances from the distance tensor

. The distance matrix construction accepts as input a

coordinate matrix

. This matrix is “neighbor listed” into a

matrix

R = tf.reduce_sum(tf.multiply(D, D), 3) # D: Distance Tensor

R = tf.sqrt(R) # R: Distance Matrix
return R

Atom type convolution

The output of the atom type convolution is constructed from the distance matrix

and atomic number matrix

. The matrix

is fed into a (1x1) filter with stride 1 and depth of

, where

is the number of unique atomic numbers (atom types) present in the molecular system. The atom type convolution
kernel is a step function that operates on the neighbor distance matrix

Radial Pooling layer

x1) with stride 1 and a depth of

, where

is the number of desired radial filters and

is the maximum number of neighbors.

Atomistic fully connected network

Atomic Convolution layers are stacked by feeding the flattened (
,

Now that we have seen the structural overview of ACNNs, we'll try to get deeper into the model and see how we can
train it and what we expect as the output.

For the training, we will use the publicly available PDBbind dataset. In this example, every row reflects a protein-ligand
complex and the target is the binding affinity (

) of the ligand to the protein in the complex.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!pip install -q condacolab

import condacolab
condacolab.install()
!/usr/local/bin/conda info -e

!/usr/local/bin/conda install -c conda-forge pycosat mdtraj pdbfixer openmm -y -q # needed for AtomicConvs

!pip install --pre deepchem

import deepchem
deepchem.__version__

import deepchem as dc
import os

import numpy as np
import tensorflow as tf

import matplotlib.pyplot as plt

from rdkit import Chem

from deepchem.molnet import load_pdbbind

from deepchem.models import AtomicConvModel
from deepchem.feat import AtomicConvFeaturizer

Getting protein-ligand data

f1_num_atoms = 100 # maximum number of atoms to consider in the ligand

f2_num_atoms = 1000 # maximum number of atoms to consider in the protein
max_num_neighbors = 12 # maximum number of spatial neighbors for an atom

acf = AtomicConvFeaturizer(frag1_num_atoms=f1_num_atoms,
frag2_num_atoms=f2_num_atoms,
complex_num_atoms=f1_num_atoms+f2_num_atoms,
max_num_neighbors=max_num_neighbors,
neighbor_cutoff=4)

%%time
tasks, datasets, transformers = load_pdbbind(featurizer=acf,
save_dir='.',
data_dir='.',
pocket=True,
reload=False,
set_name='core')

/usr/local/lib/python3.7/dist-packages/numpy/core/_asarray.py:83: VisibleDeprecationWarning: Creating an ndarray

class MyTransformer(dc.trans.Transformer):
def transform_array(x, y, w, ids):
kept_rows = x != None
return x[kept_rows], y[kept_rows], w[kept_rows], ids[kept_rows],

datasets = [d.transform(MyTransformer) for d in datasets]

datasets

train, val, test = datasets

Training the model

losses, val_losses = [], []

%%time
max_epochs = 50

acm.fit(train, nb_epoch=max_epochs, max_checkpoints_to_keep=1,

callbacks=[val_cb])

CPU times: user 2min 41s, sys: 11.4 s, total: 2min 53s
Wall time: 2min 47s

f, ax = plt.subplots()
ax.scatter(range(len(losses)), losses, label='train loss')
ax.scatter(range(len(val_losses)), val_losses, label='val loss')
plt.legend(loc='upper right');

The ACNN paper showed a Pearson

score = dc.metrics.Metric(dc.metrics.score_function.pearson_r2_score)
for tvt, ds in zip(['train', 'val', 'test'], datasets):
print(tvt, acm.evaluate(ds, metrics=[score]))

train {'pearson_r2_score': 0.9311347622675604

val {'pearson_r2_score': 0.5162870575992874}
test {'pearson_r2_score': 0.4756633065901693}

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Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Applications of DeepChem with Alphafold: Docking and
protein-ligand interaction from protein sequence
Author: Sriphani Vardhan Bellamkonda

In this tutorial, we explore a potential use case where we combine the capabilities of AlphaFold and DeepChem.

Alphafold2 has made immense strides in predicting protein structure folding without the use of costly lab equipment and
DeepChem comprises a repertoire of easy to use modules which can then be applied on these protein structures for
further analysis. In the first part of our tutorial we will predict the protein structure when given a protein sequence.
Then, in the second part of our tutorial, we sample a few ligands from the protein-complex dataset(PDBbind) and
perform programmatic docking to estimate binding affinities between our protein and a number of ligands.

This tutorial is meant to be run in google colab. You can follow the below link to open this notebook in colab.

Open in Colab

Setup
We start off with all the installations and configurations. If you would like to directly skip reading this part, you can head
over to the Input Query Section below.

We will first be installing deepchem as a runtime restart might be required. Along with that lets also install condacolab,
vina and pdbfixer which will be used in the later parts of this tutorial.

!pip install -q condacolab

import condacolab
condacolab.install()
!conda install -c conda-forge openmm -y
!mkdir vina_test

!conda install -c conda-forge pdbfixer

!conda install -c conda-forge vina
!pip install deepchem
!pip install -q mdtraj nglview

Restart may be prompted

Part 1: Predict Protein Structure in pdb format from a given input sequence
Note: The cells until part 2 of this tutorial are directly from the Colabfold's google colab implementation and have been
further annotated in this tutorial.

Alphafold Colabfold Openfold .....so many folds!

In 2020, a major breakthrough in protein structure prediction occurred when AlphaFold2, a newer version of AlphaFold,
vastly outperformed other models in the CASP (Critical Assessment of Protein Structure Prediction) competition. After
this breakthrough event, several organizations worked ahead of AlphaFold2 and provided slightly different solutions for
the protein folding problem. For example, ColabFold provides faster protein structure modeling because it uses a
separate server for the sequence alignment step of AlphaFold2, and OpenFold provides a few enhancements, such as
faster inference and custom CUDA attention kernels, while being implemented in PyTorch. Apart from these, there are
other protein folding models, such as AlphaFold-multimer, OmegaFold, and RosettaFold, designed for different
scenarios. Due to its simplicity, we will be using Colabfold in our tutorial.

ColabFold v1.5.3-patch: AlphaFold2 using MMseqs2

ColabFold is an easy to use protien structure and complex prediction model which uses Alphafold2
and Alphafold2-multimer for sequence to structure prediction of single and multiple protein chains.
It also abstracts out the Sequence Alignment/Template Generation step or MSA, Multiple Sequence
Alignemnt, through MMSeqs2 and HHsearch. MSA step is explained in more detail in the cells below.

For more details, checkout the ColabFold GitHub and read the below manuscript.

Mirdita M, Schütze K, Moriwaki Y, Heo L, Ovchinnikov S, Steinegger M. ColabFold: Making protein folding accessible to
all. Nature Methods, 2022
We then create a job-name folder and store all the sequences as queries in a text file which we will reference later to
call model inference on. The way that Alphafold is structured is that it interacts with a job directory to process the
inputs, templates, and save the outpus. Hence, it is important to create a unique job folder.

#@title Input protein sequence(s), then hit `Runtime` -> `Run all`
from google.colab import files
import os
import re
import hashlib
import random

from sys import version_info

python_version = f"{version_info.major}.{version_info.minor}"

# query_sequence = 'PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASK' #@param {type:"string"}

query_sequence='#'
#@markdown - Use `:` to specify inter-protein chainbreaks for **modeling complexes** (supports homo- and hetro-oligo
jobname = 'test' #@param {type:"string"}
# number of models to use
num_relax = 0 #@param [0, 1, 5] {type:"raw"}
#@markdown - specify how many of the top ranked structures to relax using amber

use_amber = num_relax > 0

Use the below parameter to set template configs.

AlphaFold uses templates from a vast protein structure database to guide its predictions. It aligns the target protein's
sequence with similar sequences from the database to generate structural constraints, aiding in the accurate prediction
of the protein's 3D structure.

none = no template information is used. In this case the sequence alignment step is skipped and prediction is made
without it.

pdb100 = templates are detected from the pdb100 database. pdb100 is a subset of the Protein Data Bank (PDB)
containing 100 diverse protein structures used for training and validation in structural biology and bioinformatics
research.

custom = the user has the option to upload their own templates database to search on (PDB or mmCIF format)

template_mode = "none" #@param ["none", "pdb100","custom"]

Lets specify a hashing function which we will use to create a job name. Hashing is mainly used to reduce the length of
the folder name in order to have reasonable and unique jobname everytime we run the notebook.

def add_hash(x,y):
return x+"_"+hashlib.sha1(y.encode()).hexdigest()[:5]

# remove whitespaces
query_sequence = "".join(query_sequence.split())

basejobname = "".join(jobname.split())
basejobname = re.sub(r'\W+', '', basejobname)
jobname = add_hash(basejobname, query_sequence)

We then create the directory where we will store our protein seqeunce (query) and respective files which will be
generated in the later parts of this tutorial. We also define a check function below which prevents us from creating
duplicate directories.

# check if directory with jobname exists

def check(folder):
if os.path.exists(folder):
return False
else:
return True
if not check(jobname):
n = 0
while not check(f"{jobname}_{n}"): n += 1
jobname = f"{jobname}_{n}"

# make directory to save results

os.makedirs(jobname, exist_ok=True)

Based on the template_mode specified earlier, we automatically adjust a few parameters such as use_templates and
custom_template_path. If the template_mode is custom, we will create an additional directory for it.

if template_mode == "pdb100":
use_templates = True
custom_template_path = None
elif template_mode == "custom":
custom_template_path = os.path.join(jobname,f"template")
os.makedirs(custom_template_path, exist_ok=True)
uploaded = files.upload()
use_templates = True
for fn in uploaded.keys():
os.rename(fn,os.path.join(custom_template_path,fn))
else:
custom_template_path = None
use_templates = False

Install dependencies
Based on the parameters mentioned above we will respectively install the dependencies with the code below.

1. First we have to install the latest version of ColabFold from their github repo. After a successful installation, a file
called COLABFOLD_READY will be created to mark its completion.

%%time
import os
USE_AMBER = use_amber
USE_TEMPLATES = use_templates
PYTHON_VERSION = python_version

if not os.path.isfile("COLABFOLD_READY"):
print("installing colabfold...")
os.system("pip install -q --no-warn-conflicts 'colabfold[alphafold-minus-jax] @ git+https://github.com/sokrypton/Co
os.system("pip install --upgrade dm-haiku")
os.system("ln -s /usr/local/lib/python3.*/dist-packages/colabfold colabfold")
os.system("ln -s /usr/local/lib/python3.*/dist-packages/alphafold alphafold")
# patch for jax > 0.3.25
os.system("sed -i 's/weights = jax.nn.softmax(logits)/logits=jnp.clip(logits,-1e8,1e8);weights=jax.nn.softmax(logit
os.system("touch COLABFOLD_READY")

CPU times: user 0 ns, sys: 35 µs, total: 35 µs

Wall time: 40.1 µs

2. Next, if we need amber relaxation or protein templates, we will install mamba which will help us in installing further
packages

if USE_AMBER or USE_TEMPLATES:
if not os.path.isfile("CONDA_READY"):
print("installing conda...")
os.system("wget -qnc https://github.com/conda-forge/miniforge/releases/latest/download/Mambaforge-Linux-x86_64.sh
os.system("bash Mambaforge-Linux-x86_64.sh -bfp /usr/local")
os.system("mamba config --set auto_update_conda false")
os.system("touch CONDA_READY")

3. Then, we will install hhsuite for db-search/tempate-retireval and openmm for amber relaxation.

if USE_TEMPLATES and not os.path.isfile("HH_READY") and USE_AMBER and not os.path.isfile("AMBER_READY"):

print("installing hhsuite and amber...")
os.system(f"mamba install -y -c conda-forge -c bioconda kalign2=2.04 hhsuite=3.3.0 openmm=7.7.0 python='{PYTHON_VER
os.system("touch HH_READY")
os.system("touch AMBER_READY")
else:
if USE_TEMPLATES and not os.path.isfile("HH_READY"):
print("installing hhsuite...")
os.system(f"mamba install -y -c conda-forge -c bioconda kalign2=2.04 hhsuite=3.3.0 python='{PYTHON_VERSION}'")
os.system("touch HH_READY")
if USE_AMBER and not os.path.isfile("AMBER_READY"):
print("installing amber...")
os.system(f"mamba install -y -c conda-forge openmm=7.7.0 python='{PYTHON_VERSION}' pdbfixer")
os.system("touch AMBER_READY")

A little about the softwares we are installing:

HHsuite is a widely used open source software suite for sensitive sequence similarity searches and protein fold
recognition.

Openmm is a high-performance toolkit for molecular simulation. In our tutorial this tooklkit helps us simulate amber
force field which is used to "relax" the position of atoms with respect to each other in order to remove any definite
obstructions between them. This helps us to better model protein folding in edge cases and offers better refinement of
the protein structures.
Now lets specifiy the different msa options available.

MSA
Multi Sequence Alignment is a process in Alphafold which aligns multiple sequences of amino acids from different
sources which have a similar sequence. In this step, Alphafold2 forms a grid aligning identical amino acids in the same
columns and leaving gaps where there are differences. We have the option of how we would like to pair the respective
MSA with the options: "unpaired_paired" to pair sequences from same species and an unpaired MSA, "unpaired" to
seperate MSA for each chain, and "paired" to only use paired sequences. Additionally, we have multiple options in the
way Alphafold searches for the respective sequences and few of them are mentioned below.

MMSEQ2: This is a sequence searching tool which finds similar sequences to our input sequence from a large database.

Single_sequence: This option restricts Alphafold from searching for any similar amino acid sequences and restricts it
utilize the only given one.

Custom: This options lets Alphafold do the sequence search from user defined sequence search space.

#@markdown ### MSA options (custom MSA upload, single sequence, pairing mode)
msa_mode = "mmseqs2_uniref_env" #@param ["mmseqs2_uniref_env", "mmseqs2_uniref","single_sequence","custom"]
pair_mode = "unpaired_paired" #@param ["unpaired_paired","paired","unpaired"] {type:"string"}
#@markdown - "unpaired_paired" = pair sequences from same species + unpaired MSA, "unpaired" = seperate MSA for each

So based on the above msa parameters we will set the path to the A3M file. An A3M file (Alignment to Multiple Models)
is a type of input file used in the protein structure prediction process which contains multiple sequence alignments
(MSAs) of related protein sequences that are used as input data for the AlphaFold model. A3M file format is an
extentions to FASTA file format and can be read about over at FASTA format extension.

Additionally, for the purpose of this tutorial we don't need to get into the details of custom MSA(where user inputs their
own template databse for search).

# decide which a3m to use

if "mmseqs2" in msa_mode:
a3m_file = os.path.join(jobname,f"{jobname}.a3m")

Advanced settings
Below we can specify more advanced settings with Alphafold. We can choose which model parameters to use from the
options given below i.e alphafold2, alphafold2_multimer_v1 etc.., recycle early stop tolerence, saving to google drive,
and image resolution options. Also note that there is no need to fully understand the parameters and just stick to the
defaults. But here are a few details about the parameters which can be changed.

model_type: If auto selected, will use alphafold2_ptm for monomer prediction and alphafold2_multimer_v3 for complex
prediction. Any of the mode_types can be used (regardless if input is monomer or complex).

num_recycles: "auto" with other options available as ["auto", "0", "1", "3", "6", "12", "24", "48"]

recycle_early_stop_tolerance: "auto" with other options available as ["auto", "0.0", "0.5", "1.0"]

By "recycling" Alphafold refers to the process of iterative refinement of protein structure prediction to imporve accuracy.

Pairing strategy: "greedy" or "complete"

1. greedy = pair any taxonomically matching subsets

2. complete = all sequences have to match in one line.

#@markdown ### Advanced settings

model_type = "auto" #@param ["auto", "alphafold2_ptm", "alphafold2_multimer_v1", "alphafold2_multimer_v2", "alphafold
#@markdown - if àuto` selected, will use àlphafold2_ptm` for monomer prediction and àlphafold2_multimer_v3` for co
#@markdown Any of the mode_types can be used (regardless if input is monomer or complex).
num_recycles = "3" #@param ["auto", "0", "1", "3", "6", "12", "24", "48"]
#@markdown - if àuto` selected, will use `num_recycles=20` if `model_type=alphafold2_multimer_v3`, else `num_recycle
recycle_early_stop_tolerance = "auto" #@param ["auto", "0.0", "0.5", "1.0"]
#@markdown - if àuto` selected, will use `tol=0.5` if `model_type=alphafold2_multimer_v3` else `tol=0.0`.
relax_max_iterations = 200 #@param [0, 200, 2000] {type:"raw"}
#@markdown - max amber relax iterations, `0` = unlimited (AlphaFold2 default, can take very long)
pairing_strategy = "greedy" #@param ["greedy", "complete"] {type:"string"}
#@markdown - `greedy` = pair any taxonomically matching subsets, `complete` = all sequences have to match in one line

We can also set the maximum length of Multiple Sequence Alignment, Number of Seeds, and whether to use dropout or
not.
max_msa = "auto" with other optinos as ["auto", "512:1024", "256:512", "64:128", "32:64", "16:32"]. Here left is the
minimum and right is the maximum msa length.

num_seeds = 1 with other options as [1,2,4,8,16] {type:"raw"}

use_dropout = False other option True

#@markdown #### Sample settings

#@markdown - enable dropouts and increase number of seeds to sample predictions from uncertainty of the model.
#@markdown - decrease `max_msa` to increase uncertainity
max_msa = "auto" #@param ["auto", "512:1024", "256:512", "64:128", "32:64", "16:32"]
num_seeds = 1 #@param [1,2,4,8,16] {type:"raw"}
use_dropout = False #@param {type:"boolean"}

num_recycles = None if num_recycles == "auto" else int(num_recycles)

recycle_early_stop_tolerance = None if recycle_early_stop_tolerance == "auto" else float(recycle_early_stop_tolerance
if max_msa == "auto": max_msa = None

Save to Google Drive

We define a simple save_to_google_drive function which authenticates into our respective google drive and allows to
save our files.

#@markdown #### Save settings

save_all = False #@param {type:"boolean"}
save_recycles = False #@param {type:"boolean"}
save_to_google_drive = False #@param {type:"boolean"}
#@markdown - if the save_to_google_drive option was selected, the result zip will be uploaded to your Google Drive
dpi = 200 #@param {type:"integer"}
#@markdown - set dpi for image resolution

if save_to_google_drive:
from pydrive.drive import GoogleDrive
from pydrive.auth import GoogleAuth
from google.colab import auth
from oauth2client.client import GoogleCredentials
auth.authenticate_user()
gauth = GoogleAuth()
gauth.credentials = GoogleCredentials.get_application_default()
drive = GoogleDrive(gauth)
print("You are logged into Google Drive and are good to go!")

Now we will run the prediction model using all the inputs and specifications from above.

We import the respective files from Colabfold's package for inference and plotting, and we then check if we have a
specific GPU. We also define 2 helper functions: input_features_callback, and prediction_callback, which help us to
visualize the respective input featues and prediction results.

Lets import utility, batch and plotting functions from colabfold!

#@title Run Prediction

display_images = True #@param {type:"boolean"}

import sys
import warnings
warnings.simplefilter(action='ignore', category=FutureWarning)
from Bio import BiopythonDeprecationWarning
warnings.simplefilter(action='ignore', category=BiopythonDeprecationWarning)
from pathlib import Path
from colabfold.download import download_alphafold_params, default_data_dir
from colabfold.utils import setup_logging
from colabfold.batch import get_queries, run, set_model_type
from colabfold.plot import plot_msa_v2

import os
import numpy as np

Next we check if K80 GPU is available.

try:
K80_chk = os.popen('nvidia-smi | grep "Tesla K80" | wc -l').read()
except:
K80_chk = "0"
pass
if "1" in K80_chk:
print("WARNING: found GPU Tesla K80: limited to total length < 1000")
if "TF_FORCE_UNIFIED_MEMORY" in os.environ:
del os.environ["TF_FORCE_UNIFIED_MEMORY"]
if "XLA_PYTHON_CLIENT_MEM_FRACTION" in os.environ:
del os.environ["XLA_PYTHON_CLIENT_MEM_FRACTION"]

Now, let's define some helper functions to visualize input features and output preduction.

from colabfold.colabfold import plot_protein

from pathlib import Path
import matplotlib.pyplot as plt

# For some reason we need that to get pdbfixer to import

if use_amber and f"/usr/local/lib/python{python_version}/site-packages/" not in sys.path:
sys.path.insert(0, f"/usr/local/lib/python{python_version}/site-packages/")

def input_features_callback(input_features):
if display_images:
plot_msa_v2(input_features)
plt.show()
plt.close()

def prediction_callback(protein_obj, length,

prediction_result, input_features, mode):
model_name, relaxed = mode
if not relaxed:
if display_images:
fig = plot_protein(protein_obj, Ls=length, dpi=150)
plt.show()
plt.close()

Let's define our logging environment and retrieve the input queries from our job folder.

result_dir = jobname
log_filename = os.path.join(jobname,"log.txt")
setup_logging(Path(log_filename))

Input Query Sequence

Lets specify our input for Sequence to Structure prediction. We should specify the input sequence (seperated by ':' for
specifying inter-protein chain breaks to model complexes) and whether we would like to use amber relaxation or not.

query_sequence = 'PIAQIHILEGRSDEQKETLIREVSEAISRSLDAPLTSVRVIITEMAKGHFGIGGELASK' #@param {type:"string"}

We then store our query_sequence in a csv inside the jobname director. This facilates multiple query execution and
provides input in the format expected by ColabFold.

# save queries
queries_path = os.path.join(jobname, f"{jobname}.csv")
with open(queries_path, "w") as text_file:
text_file.write(f"id,sequence\n{jobname},{query_sequence}")

We utilize the get_queries function, which is a colabfold utility function, to fetch the queries from the directory.

One downside to having a high number of sequence alignemts(~128) detected in the MSA step is that it is
quadrateically expensive to continue the later steps in inference. In order, to reduce this the MSA's are clustered
smartly, based on sequence similarity, in order to reduce the computational cost while ensuring that each MSA has
some influence on the final prediction. This clustering step is captured by use_cluster_profile which is also configured
below.

queries, is_complex = get_queries(queries_path)

model_type = set_model_type(is_complex, model_type)

if "multimer" in model_type and max_msa is not None:

use_cluster_profile = False
else:
use_cluster_profile = True

Inference
Our final step is to download the alphafold parameters for the model and run inference using all the previous given
specifications and inputs.

We will then save the results in a zip file and download it.

download_alphafold_params(model_type, Path("."))
results = run(
queries=queries,
result_dir=result_dir,
use_templates=use_templates,
custom_template_path=custom_template_path,
num_relax=num_relax,
msa_mode=msa_mode,
model_type=model_type,
num_models=5,
num_recycles=num_recycles,
relax_max_iterations=relax_max_iterations,
recycle_early_stop_tolerance=recycle_early_stop_tolerance,
num_seeds=num_seeds,
use_dropout=use_dropout,
model_order=[1,2,3,4,5],
is_complex=is_complex,
data_dir=Path("."),
keep_existing_results=False,
rank_by="auto",
pair_mode=pair_mode,
pairing_strategy=pairing_strategy,
stop_at_score=float(100),
prediction_callback=prediction_callback,
dpi=dpi,
zip_results=False,
save_all=save_all,
max_msa=max_msa,
use_cluster_profile=use_cluster_profile,
input_features_callback=input_features_callback,
save_recycles=save_recycles,
user_agent="colabfold/google-colab-main",
)
results_zip = f"{jobname}.result.zip"
os.system(f"zip -r {results_zip} {jobname}")

2023-11-14 00:35:33,396 Running on GPU

2023-11-14 00:35:33,401 Found 4 citations for tools or databases
2023-11-14 00:35:33,401 Query 1/1: test_d08f8 (length 59)
COMPLETE: 100%|██████████| 150/150 [elapsed: 00:02 remaining: 00:00]

2023-11-14 00:35:37,107 Setting max_seq=512, max_extra_seq=5120

2023-11-14 00:35:58,595 alphafold2_ptm_model_1_seed_000 recycle=0 pLDDT=96.6 pTM=0.755
2023-11-14 00:36:01,632 alphafold2_ptm_model_1_seed_000 recycle=1 pLDDT=96.6 pTM=0.758 tol=0.311
2023-11-14 00:36:04,668 alphafold2_ptm_model_1_seed_000 recycle=2 pLDDT=96.4 pTM=0.757 tol=0.043
2023-11-14 00:36:07,706 alphafold2_ptm_model_1_seed_000 recycle=3 pLDDT=96.2 pTM=0.757 tol=0.0399
2023-11-14 00:36:07,708 alphafold2_ptm_model_1_seed_000 took 25.1s (3 recycles)
2023-11-14 00:36:10,843 alphafold2_ptm_model_2_seed_000 recycle=0 pLDDT=96.9 pTM=0.76
2023-11-14 00:36:13,881 alphafold2_ptm_model_2_seed_000 recycle=1 pLDDT=96.9 pTM=0.765 tol=0.375
2023-11-14 00:36:16,920 alphafold2_ptm_model_2_seed_000 recycle=2 pLDDT=96.9 pTM=0.766 tol=0.12
2023-11-14 00:36:19,959 alphafold2_ptm_model_2_seed_000 recycle=3 pLDDT=96.8 pTM=0.767 tol=0.0779
2023-11-14 00:36:19,960 alphafold2_ptm_model_2_seed_000 took 12.2s (3 recycles)

2023-11-14 00:36:23,114 alphafold2_ptm_model_3_seed_000 recycle=0 pLDDT=97.2 pTM=0.775

2023-11-14 00:36:26,153 alphafold2_ptm_model_3_seed_000 recycle=1 pLDDT=97.4 pTM=0.782 tol=0.297
2023-11-14 00:36:29,190 alphafold2_ptm_model_3_seed_000 recycle=2 pLDDT=97.4 pTM=0.782 tol=0.105
2023-11-14 00:36:32,230 alphafold2_ptm_model_3_seed_000 recycle=3 pLDDT=97.4 pTM=0.784 tol=0.0659
2023-11-14 00:36:32,231 alphafold2_ptm_model_3_seed_000 took 12.2s (3 recycles)
2023-11-14 00:36:35,372 alphafold2_ptm_model_4_seed_000 recycle=0 pLDDT=97.4 pTM=0.775
2023-11-14 00:36:38,411 alphafold2_ptm_model_4_seed_000 recycle=1 pLDDT=97.4 pTM=0.781 tol=0.282
2023-11-14 00:36:41,451 alphafold2_ptm_model_4_seed_000 recycle=2 pLDDT=97.2 pTM=0.778 tol=0.0839
2023-11-14 00:36:44,490 alphafold2_ptm_model_4_seed_000 recycle=3 pLDDT=97.1 pTM=0.779 tol=0.0421
2023-11-14 00:36:44,491 alphafold2_ptm_model_4_seed_000 took 12.2s (3 recycles)

2023-11-14 00:36:47,670 alphafold2_ptm_model_5_seed_000 recycle=0 pLDDT=97.4 pTM=0.784

2023-11-14 00:36:50,712 alphafold2_ptm_model_5_seed_000 recycle=1 pLDDT=96.9 pTM=0.784 tol=0.237
2023-11-14 00:36:53,750 alphafold2_ptm_model_5_seed_000 recycle=2 pLDDT=96.3 pTM=0.777 tol=0.18
2023-11-14 00:36:56,788 alphafold2_ptm_model_5_seed_000 recycle=3 pLDDT=96.2 pTM=0.777 tol=0.121
2023-11-14 00:36:56,789 alphafold2_ptm_model_5_seed_000 took 12.2s (3 recycles)
2023-11-14 00:36:56,927 reranking models by 'plddt' metric
2023-11-14 00:36:56,927 rank_001_alphafold2_ptm_model_3_seed_000 pLDDT=97.4 pTM=0.784
2023-11-14 00:36:56,929 rank_002_alphafold2_ptm_model_4_seed_000 pLDDT=97.1 pTM=0.779
2023-11-14 00:36:56,930 rank_003_alphafold2_ptm_model_2_seed_000 pLDDT=96.8 pTM=0.767
2023-11-14 00:36:56,930 rank_004_alphafold2_ptm_model_1_seed_000 pLDDT=96.2 pTM=0.757
2023-11-14 00:36:56,931 rank_005_alphafold2_ptm_model_5_seed_000 pLDDT=96.2 pTM=0.777
2023-11-14 00:36:58,495 Done
0

Display 3D structure of the protein file generated based on a few options and using
py3Dmol package
Alphafold generates top n ranked model estimates of the protein structure. Here we have 5 ranked structures. The lower
the rank the higher the accuracy and quality of the predicted model.

Here we can display the structure with various color schemas: chair, lDDT, and rainbow. We also have options to show
the sidechain and mainchains of the protein's structure.

Let's import a few important visualization libraries and set the visualization variables.

#@title Display 3D structure {run: "auto"}

import py3Dmol
import glob
import matplotlib.pyplot as plt
from colabfold.colabfold import plot_plddt_legend
from colabfold.colabfold import pymol_color_list, alphabet_list
rank_num = 1 #@param ["1", "2", "3", "4", "5"] {type:"raw"}
color = "lDDT" #@param ["chain", "lDDT", "rainbow"]
show_sidechains = False #@param {type:"boolean"}
show_mainchains = False #@param {type:"boolean"}

tag = results["rank"][0][rank_num - 1]
jobname_prefix = ".custom" if msa_mode == "custom" else ""
pdb_filename = f"{jobname}/{jobname}{jobname_prefix}_unrelaxed_{tag}.pdb"
pdb_file = glob.glob(pdb_filename)

Capture the protein structure

Let us store the file path to the generated protein structure so that we can utilize it in the second part of our tutorial for
pocket finding and protein-ligand interactions!

print("Files generated: ", pdb_filename, pdb_file)

pdb_filename_captured = pdb_filename
Files generated: test_a5e17_0/test_a5e17_0_unrelaxed_rank_001_alphafold2_ptm_model_3_seed_000.pdb ['test_a5e17_
0/test_a5e17_0_unrelaxed_rank_001_alphafold2_ptm_model_3_seed_000.pdb']

Now lets define the visualization function show_pdb using py3Dmol. This function takes in the pdb and various
visualization parameters such as rank number, sidechains, and mainchains and visualizes the protein accordingly Here
we have passed "lDDT" for the color parameter of the function. lDDT is in short for local Distance Difference Test. We
display the color based on the score for each part of the protein as mentioned in the key of the .

def show_pdb(rank_num=1, show_sidechains=False, show_mainchains=False, color="lDDT"):

model_name = f"rank_{rank_num}"
view = py3Dmol.view(js='https://3dmol.org/build/3Dmol.js',)
view.addModel(open(pdb_file[0],'r').read(),'pdb')

if color == "lDDT":
view.setStyle({'cartoon': {'colorscheme': {'prop':'b','gradient': 'roygb','min':50,'max':90}}})
elif color == "rainbow":
view.setStyle({'cartoon': {'color':'spectrum'}})
elif color == "chain":
chains = len(queries[0][1]) + 1 if is_complex else 1
for n,chain,color in zip(range(chains),alphabet_list,pymol_color_list):
view.setStyle({'chain':chain},{'cartoon': {'color':color}})

if show_sidechains:
BB = ['C','O','N']
view.addStyle({'and':[{'resn':["GLY","PRO"],'invert':True},{'atom':BB,'invert':True}]},
{'stick':{'colorscheme':f"WhiteCarbon",'radius':0.3}})
view.addStyle({'and':[{'resn':"GLY"},{'atom':'CA'}]},
{'sphere':{'colorscheme':f"WhiteCarbon",'radius':0.3}})
view.addStyle({'and':[{'resn':"PRO"},{'atom':['C','O'],'invert':True}]},
{'stick':{'colorscheme':f"WhiteCarbon",'radius':0.3}})
if show_mainchains:
BB = ['C','O','N','CA']
view.addStyle({'atom':BB},{'stick':{'colorscheme':f"WhiteCarbon",'radius':0.3}})

view.zoomTo()
return view

show_pdb(rank_num, show_sidechains, show_mainchains, color).show()

if color == "lDDT":
plot_plddt_legend().show()

PLOTS of Alphafold
The following 3 types of plots are generated with Alphafold.

1. PAE (Predicted Average Error): It measures the average error in the predicted atomic positions of a protein's 3D
structure compared to the true positions. In our experiment below, the PAE plot of the top 5 ranked sturctures is
mostly blue which means that we have low errors.
2. COV (Sequence Coverage): It indicates the percentage of aminoacid sequence for which Alphafold has provided
structural prediction and to what degree. In the plot below, the x-axis represents the amino acid sequence and the
y-axis represents the number sequences for that amino acid.

3. iDDT (local Distance Difference Test) or lDDT: It provides a per-residue measure of the predicted model's
confidence. It assigns a score to each residue in the protein structure, indicating the reliability of the prediction at
that location. For our protein sequence the lDDT is high throughout the amino acid sequence but tends to get lower
towards the right end.

#@title Plots {run: "auto"}

from IPython.display import display, HTML
import base64
from html import escape

# see: https://stackoverflow.com/a/53688522
def image_to_data_url(filename):
ext = filename.split('.')[-1]
prefix = f'data:image/{ext};base64,'
with open(filename, 'rb') as f:
img = f.read()
return prefix + base64.b64encode(img).decode('utf-8')

pae = image_to_data_url(os.path.join(jobname,f"{jobname}{jobname_prefix}_pae.png"))
cov = image_to_data_url(os.path.join(jobname,f"{jobname}{jobname_prefix}_coverage.png"))
plddt = image_to_data_url(os.path.join(jobname,f"{jobname}{jobname_prefix}_plddt.png"))
display(HTML(f"""
<style>
img {{
float:left;
}}
.full {{
max-width:100%;
}}
.half {{
max-width:50%;
}}
@media (max-width:640px) {{
.half {{
max-width:100%;
}}
}}
</style>
<div style="max-width:90%; padding:2em;">
<h1>Plots for {escape(jobname)}</h1>
<img src="{pae}" class="full" />
<img src="{cov}" class="half" />
<img src="{plddt}" class="half" />
</div>
"""))

Plots for test_d08f8

Package and download results(optional)
The below code can be used to download the generated zip folder to your local system or saved to google drive.

if msa_mode == "custom":
print("Don't forget to cite your custom MSA generation method.")

files.download(f"{jobname}.result.zip")

if save_to_google_drive == True and drive:

uploaded = drive.CreateFile({'title': f"{jobname}.result.zip"})
uploaded.SetContentFile(f"{jobname}.result.zip")
uploaded.Upload()
print(f"Uploaded {jobname}.result.zip to Google Drive with ID {uploaded.get('id')}")

Part 2: Estimate binding affinities between the predicted

protein and a sample set of ligands
Let's import deepchem utility functions and rdkit which helps us in visualization.

import os
import numpy as np
import pandas as pd

import tempfile

from rdkit import Chem

from rdkit.Chem import AllChem

import deepchem as dc
from deepchem.utils import download_url, load_from_disk

2023-11-14 00:45:56,266 Enabling RDKit 2023.09.1 jupyter extensions

2023-11-14 00:46:00,469 Skipped loading modules with pytorch-geometric dependency, missing a dependency. No modu
le named 'torch_geometric'
2023-11-14 00:46:00,471 Skipped loading modules with pytorch-geometric dependency, missing a dependency. cannot
import name 'DMPNN' from 'deepchem.models.torch_models' (/usr/local/lib/python3.10/site-packages/deepchem/models
/torch_models/__init__.py)
2023-11-14 00:46:00,473 Skipped loading modules with pytorch-lightning dependency, missing a dependency. No modu
le named 'pytorch_lightning'

To sample a set of ligands we will use PDBind. We will download the respective dataset file and store it in a variable
called raw_dataset.

data_dir = dc.utils.get_data_dir()
dataset_file = os.path.join(data_dir, "pdbbind_core_df.csv.gz")

raw_dataset = load_from_disk(dataset_file)
raw_dataset = raw_dataset[['pdb_id', 'smiles', 'label']]

from openmm.app import PDBFile

from pdbfixer import PDBFixer

from deepchem.utils.vina_utils import prepare_inputs

File does not exist. Downloading file...

File downloaded...

Pocket finding in the predicted protein structure

By utilizing DeepChem's docking modules we can find the number of pockets in the generated structure. We do so by
utilizing the 3D-ConvexHullPocketFinder.

ligands10 = raw_dataset['smiles'].iloc[0:10]

# %%time
import os
#'test_a5e17/test_a5e17_unrelaxed_rank_001_alphafold2_ptm_model_3_seed_000.pdb'
generated_pdb = pdb_filename_captured
generated_pdb_no_extension = os.path.splitext(os.path.basename(generated_pdb))[0]

finder = dc.dock.binding_pocket.ConvexHullPocketFinder()
pockets = finder.find_pockets(generated_pdb)

print("Pockets for protein: " + str(len(pockets)) ) # number of identified pockets

Pockets for protein: 8

Docking with Vina Pose Generator

For docking the protein and ligand, we will be using DeepChem's VinaPoseGenerator which automatically installs
AutoDock Vina engine and allows us to seamlessly use it. And before we dock a given ligand and protein we have to
ensure that the inputs are reasonable for docking which is also handled by a DeepChem's utility function called
prepare_inputs. It fixes the protein geometry, optimizes ligand geometry, and sanitizes the molecules. Next, we
generate the complex combining the protein and ligand and then display the scores. Analysis of the scores of the
combined complex is printed below. For the sake of simplicity, we will be iterating over 3 ligands and comparing the
complex scores.
import locale
locale.getpreferredencoding = lambda: "UTF-8"
!mkdir results

vpg = dc.dock.pose_generation.VinaPoseGenerator()
count=0
scores_matrix =[]
complex_mol_array = []
for count in range(0,3):
print("Docking ligand "+str(count))
ligand = ligands10[count]
p, m = None, None

vpg = dc.dock.pose_generation.VinaPoseGenerator()

try:
p, m = prepare_inputs('%s' % (generated_pdb), ligand)
except:
print('%s failed PDB fixing' % (generated_pdb))

if p and m: # protein and molecule are readable by RDKit

print(generated_pdb, p.GetNumAtoms())
Chem.rdmolfiles.MolToPDBFile(p, 'results/protein_%s.pdb' % (count))
Chem.rdmolfiles.MolToPDBFile(m, 'results/ligand_%s.pdb' % (count))

complexes, scores = vpg.generate_poses(molecular_complex=('results/protein_%s.pdb' % (count),'results/ligand_%s.pdb

out_dir='vina_test',
generate_scores=True
)
complex_mol = Chem.CombineMols(complexes[0][0], complexes[0][1])
complex_mol_array.append(complex_mol)
print(scores)
scores_matrix.append(scores)

Docking ligand 0
<ipython-input-42-a86da5d11cfe>:17: DeprecationWarning: Call to deprecated function prepare_inputs. Please use t
he corresponding function in deepchem.utils.docking_utils.
p, m = prepare_inputs('%s' % (generated_pdb), ligand)
[00:47:58] UFFTYPER: Unrecognized atom type: S_5+4 (7)
test_a5e17_0/test_a5e17_0_unrelaxed_rank_001_alphafold2_ptm_model_3_seed_000.pdb 448
2023-11-14 00:48:01,498 Pockets not specified. Will use whole protein to dock
2023-11-14 00:48:03,344 Docking in pocket 1/1
2023-11-14 00:48:03,345 Docking with center: [0.28462623 1.04385902 1.65269617]
2023-11-14 00:48:03,345 Box dimensions: [45.593 35.786 38.447]
2023-11-14 00:48:03,346 About to call Vina
/usr/local/lib/python3.10/site-packages/vina/vina.py:260: DeprecationWarning: `np.int` is a deprecated alias for
the builtin ìnt`. To silence this warning, use ìnt` by itself. Doing this will not modify any behavior and is
safe. When replacing `np.int`, you may wish to use e.g. `np.int64` or `np.int32` to specify the precision. If yo
u wish to review your current use, check the release note link for additional information.
Deprecated in NumPy 1.20; for more details and guidance: https://numpy.org/devdocs/release/1.20.0-notes.html#dep
recations
self._voxels = np.ceil(np.array(box_size) / self._spacing).astype(np.int)
<ipython-input-42-a86da5d11cfe>:17: DeprecationWarning: Call to deprecated function prepare_inputs. Please use t
he corresponding function in deepchem.utils.docking_utils.
p, m = prepare_inputs('%s' % (generated_pdb), ligand)
[-4.321, -4.142, -4.135, -4.109, -4.083, -4.069, -4.046, -4.036, -3.993]
Docking ligand 1
test_a5e17_0/test_a5e17_0_unrelaxed_rank_001_alphafold2_ptm_model_3_seed_000.pdb 448
2023-11-14 00:49:13,834 Pockets not specified. Will use whole protein to dock
2023-11-14 00:49:15,455 Docking in pocket 1/1
2023-11-14 00:49:15,457 Docking with center: [0.28062951 1.0434776 1.64895082]
2023-11-14 00:49:15,457 Box dimensions: [45.662 35.909 38.417]
2023-11-14 00:49:15,458 About to call Vina
/usr/local/lib/python3.10/site-packages/vina/vina.py:260: DeprecationWarning: `np.int` is a deprecated alias for
the builtin ìnt`. To silence this warning, use ìnt` by itself. Doing this will not modify any behavior and is
safe. When replacing `np.int`, you may wish to use e.g. `np.int64` or `np.int32` to specify the precision. If yo
u wish to review your current use, check the release note link for additional information.
Deprecated in NumPy 1.20; for more details and guidance: https://numpy.org/devdocs/release/1.20.0-notes.html#dep
recations
self._voxels = np.ceil(np.array(box_size) / self._spacing).astype(np.int)
<ipython-input-42-a86da5d11cfe>:17: DeprecationWarning: Call to deprecated function prepare_inputs. Please use t
he corresponding function in deepchem.utils.docking_utils.
p, m = prepare_inputs('%s' % (generated_pdb), ligand)
[-6.083, -6.022, -5.811, -5.797, -5.796, -5.73, -5.689, -5.654, -5.643]
Docking ligand 2
test_a5e17_0/test_a5e17_0_unrelaxed_rank_001_alphafold2_ptm_model_3_seed_000.pdb 448
2023-11-14 00:55:55,258 Pockets not specified. Will use whole protein to dock
2023-11-14 00:55:56,761 Docking in pocket 1/1
2023-11-14 00:55:56,762 Docking with center: [0.28300874 1.0426 1.64975847]
2023-11-14 00:55:56,762 Box dimensions: [45.657 35.819 38.429]
2023-11-14 00:55:56,763 About to call Vina
[-5.96, -5.9, -5.791, -5.733, -5.704, -5.662, -5.617, -5.605, -5.591]
/usr/local/lib/python3.10/site-packages/vina/vina.py:260: DeprecationWarning: `np.int` is a deprecated alias for
the builtin ìnt`. To silence this warning, use ìnt` by itself. Doing this will not modify any behavior and is
safe. When replacing `np.int`, you may wish to use e.g. `np.int64` or `np.int32` to specify the precision. If yo
u wish to review your current use, check the release note link for additional information.
Deprecated in NumPy 1.20; for more details and guidance: https://numpy.org/devdocs/release/1.20.0-notes.html#dep
recations
self._voxels = np.ceil(np.array(box_size) / self._spacing).astype(np.int)

Visualize the Protein ligand Complex!

We will use nglview to display the complex which we have stored previously. We add
output.enable_custom_widget_manager() so that we can run nglview in colab.

from google.colab import output

import mdtraj as md
import nglview

from IPython.display import display, Image

output.enable_custom_widget_manager()

Now lets visualize the first 3 protein ligand complexes which we have stored in the complex_mol_array

v = nglview.show_rdkit(complex_mol_array[0])
display(v)

v = nglview.show_rdkit(complex_mol_array[1])
display(v)

v = nglview.show_rdkit(complex_mol_array[2])
display(v)
print(scores_matrix)

[[-4.321, -4.142, -4.135, -4.109, -4.083, -4.069, -4.046, -4.036, -3.993], [-6.083, -6.022, -5.811, -5.797, -5.7
96, -5.73, -5.689, -5.654, -5.643], [-5.96, -5.9, -5.791, -5.733, -5.704, -5.662, -5.617, -5.605, -5.591]]

Next, we can see that all the scores generated from Vina Pose Generator for the respective complexes are negative.
This is because protein–ligand binding occurs only when the change in Gibbs free energy (ΔG) of the system is negative
and more negative the free energy is the more stable the complex would be as show in Ref. Additionally, molecular
docking evaluation based on the paper here showed that the binding affinities of all the derivatives range from (- 3.2
and -18.5 kcal/mol).

Hence based on our experiment we can successfully predict the potential affinity between a protein sequence and a
ligand even of we just have the protein sequence!

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{DeepChemXAlphafold,
title={Applications of DeepChem with Alphafold: Docking and protein-ligand interaction from
protein sequence},
organization={DeepChem},
author={Bellamkonda, Sriphani Vardhan},
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/DeepChemXAlphafold.ipynb}},

year={2023},
}
UniProt data pre-processing for binding site prediction
downstream task
This notebook guides you through:

Downloading Data: Retrieve information from the UniProt website, including details on protein families, binding
sites, active sites, and amino acid sequences.
Processing Data: Handle special symbols (angle brackets and question marks) in binding/active site information
and convert this data into binary labels. Each amino acid position in the protein sequences is marked as 1
(binding/active site) or 0 (non-binding/active site).
✂ Splitting Data: Divide amino acid sequences and their labels into stratified train/test sets based on UniProt
protein families.
Chunking Sequences: Split sequences and their labels into non-overlapping chunks of a specified length to
define a context window for the ESM-2 model.

This tutorial is made to run without any GPU support, and can be used in Google colab. If you'd like to open this
notebook in colab, you can use the following link.

Open in Colab

Download from UniProt

Let's first download a dataset of proteins from UniProt. We will obtain a TSV (Tab-Separated Values) file with specific
columns such as Protein families, Binding site, Active site, and Sequence. You can achieve this following these steps:

Go to the UniProt website and perform a search to query for the proteins of interest (you can search by organism,
protein name, function, etc). Filter your results with the filters on the left-hand side to refine your results further if
necessary. Here I performed the search: (organism_id:9606) AND (family:kinase) AND (existence:1 OR existence:2)
in UniProtKB.

Select columns: Above the search results, there is an option to select the columns you want to be included in your
download. Click on the 'Columns' button and a dropdown menu will appear.

Customize columns: In the dropdown menu, you can check the boxes next to the columns you want to include in
your TSV file. Look for the 'Protein families', 'Binding site', 'Active site', and 'Sequence' options. I also added further
info such as entry name, protein name, gene name, organism, sequence length and whether the entry has been
reviewed.

Download the file: After selecting the desired columns, click the 'Download' button located above the search results.
Choose the 'Tab-separated' format from the list of available formats. You may also have the option to select the
number of entries you want to download (e.g., all entries, displayed entries, or a custom range). Click on the
'Download' button to start the download process and your browser will prompt you to save the TSV file.

Process data
Now, let's process the downloaded UniProt TSV file with columns (Protein families, Binding site, Active site, Sequence). If
the family annotation or binding sites are missing, the code will filter out this sequence. If the Active site annotation is
missing, the sequence will be included without issue. Missing sequences are not handled by this notebook.

But first, let's set up the environment:

!pip install pandas

!pip install numpy
!pip install requests
Requirement already satisfied: pandas in /usr/local/lib/python3.10/dist-packages (2.0.3)
Requirement already satisfied: python-dateutil>=2.8.2 in /usr/local/lib/python3.10/dist-packages (from pandas) (
2.8.2)
Requirement already satisfied: pytz>=2020.1 in /usr/local/lib/python3.10/dist-packages (from pandas) (2023.4)
Requirement already satisfied: tzdata>=2022.1 in /usr/local/lib/python3.10/dist-packages (from pandas) (2024.1)
Requirement already satisfied: numpy>=1.21.0 in /usr/local/lib/python3.10/dist-packages (from pandas) (1.25.2)
Requirement already satisfied: six>=1.5 in /usr/local/lib/python3.10/dist-packages (from python-dateutil>=2.8.2-
>pandas) (1.16.0)
Requirement already satisfied: numpy in /usr/local/lib/python3.10/dist-packages (1.25.2)
Requirement already satisfied: requests in /usr/local/lib/python3.10/dist-packages (2.31.0)
Requirement already satisfied: charset-normalizer<4,>=2 in /usr/local/lib/python3.10/dist-packages (from request
s) (3.3.2)
Requirement already satisfied: idna<4,>=2.5 in /usr/local/lib/python3.10/dist-packages (from requests) (3.7)
Requirement already satisfied: urllib3<3,>=1.21.1 in /usr/local/lib/python3.10/dist-packages (from requests) (2.
0.7)
Requirement already satisfied: certifi>=2017.4.17 in /usr/local/lib/python3.10/dist-packages (from requests) (20
24.7.4)

# I/O
import pandas as pd
import numpy as np
import re
import random
import pickle
import os
import requests
import xml.etree.ElementTree as ET
# set seed
random.seed(42)
np.random.seed(42)

If you upload the downloaded file from UniProt to Google Drive, you should be able to access it by first mounting your
Google Drive and then loading it:

from google.colab import drive

drive.mount('/content/gdrive')

Mounted at /content/gdrive

# Load the dataset

file_path = "/content/gdrive/MyDrive/ESMbind/data/uniprotkb_data_2024_05_29.tsv"
data = pd.read_csv(file_path, sep='\t')
data.head()

Gene Protein
Entry Reviewed Entry Name Protein names Organism
Names families

Diacylglycerol
Homo Eukaryotic
kinase (DAG
0 A0A087WV00 unreviewed A0A087WV00_HUMAN DGKI sapiens diacylglycerol MDAAGRGCHLLPLPAA
kinase) (EC
(Human) kinase family
2.7.1.107)

Protein
kinase
CDK5 Homo
Cell division superfamily,
1 A0A090N7W4 unreviewed A0A090N7W4_HUMAN hCG_18690 sapiens MQKYEKLEKIGEGTYG
protein kinase 5 CMGC
tcag7.772 (Human)
Ser/Thr
prote...

Protein
Serine/threonine- Homo kinase
2 A0A0S2Z310 unreviewed A0A0S2Z310_HUMAN protein kinase ACVRL1 sapiens superfamily, MTLGSPRKGLLMLLMA
receptor (EC 2... (Human) TKL Ser/Thr
protei...

Protein
non-specific
Homo kinase
serine/threonine
3 A0A0S2Z4D1 unreviewed A0A0S2Z4D1_HUMAN STK11 sapiens superfamily, MEVVDPQQLGMFTE
protein kinase
(Human) CAMK Ser/Thr
(...
prote...

Protein
Rho-associated Homo kinase
4 A0A2P9DU05 unreviewed A0A2P9DU05_HUMAN protein kinase ROCK2 sapiens superfamily, MSRPPPTGKMPGAPE
(EC 2.7.11.1) (Human) AGC Ser/Thr
protei...

Now let's extract the required information for the purposes of this task: Protein families, Binding site, Active site,
Sequence. Also, let's filter out entries without binding site or protein families information.

data["Binding site"]
0 NaN
1 BINDING
33; /ligand="ATP"; /ligand_id="ChEBI:C...
2 BINDING
229; /ligand="ATP"; /ligand_id="ChEBI:...
3 BINDING
78; /ligand="ATP"; /ligand_id="ChEBI:C...
4 BINDING
121; /ligand="ATP"; /ligand_id="ChEBI:...
...
2186 NaN
2187 NaN
2188 NaN
2189 BINDING 73; /ligand="ATP"; /ligand_id="ChEBI:C...
2190 BINDING 165; /ligand="ATP"; /ligand_id="ChEBI:...
Name: Binding site, Length: 2191, dtype: object

data = data[["Entry", "Protein families", "Binding site", "Active site", "Sequence"]]

# Filter out rows with NaN values in the 'Protein families' column nor the 'Binding site' column nor the 'Sequence' c
data = data[pd.notna(data['Protein families']) & pd.notna(data['Binding site']) & pd.notna(data['Sequence'])]
print(data.shape)
data.head()

(1406, 5)
Protein
Entry Binding site Active site Sequence
families

Protein
kinase
BINDING 33;
superfamily,
1 A0A090N7W4 /ligand="ATP"; NaN MQKYEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEGVPS...
CMGC
/ligand_id="ChEBI:C...
Ser/Thr
prote...

Protein
kinase BINDING 229;
2 A0A0S2Z310 superfamily, /ligand="ATP"; NaN MTLGSPRKGLLMLLMALVTQGDPVKPSRGPLVTCTCESPHCKGPTC...
TKL Ser/Thr /ligand_id="ChEBI:...
protei...

Protein
kinase
BINDING 78;
superfamily,
3 A0A0S2Z4D1 /ligand="ATP"; NaN MEVVDPQQLGMFTEGELMSVGMDTFIHRIDSTEVIYQPRRKRAKLI...
CAMK
/ligand_id="ChEBI:C...
Ser/Thr
prote...

Protein ACT_SITE
kinase BINDING 121; 214;
4 A0A2P9DU05 superfamily, /ligand="ATP"; /note="Proton MSRPPPTGKMPGAPETAPGDGAGASRQRKLEALIRDPRSPINVESL...
AGC Ser/Thr /ligand_id="ChEBI:... acceptor";
protei... /eviden...

Protein ACT_SITE
kinase BINDING 250..258; 379;
5 A3QNQ0 superfamily, /ligand="ATP"; /note="Proton MGRGLLRGLWPLHIVLWTRIASTIPPHVQKSVNNDMIVTDNNGAVK...
TKL Ser/Thr /ligand_id="C... acceptor";
protei... /eviden...

So we have a dataset of 1406 proteins, all having a binding site and information of the aminoacids sequence and the
protein family. We download proteins proteins from human and kinase family, however there may still exist subgroups
of protein families:

# Group the data by 'Protein families' and get the size of each group
family_sizes = data.groupby('Protein families').size()
print(family_sizes.sort_values(ascending=False))

# Create a new column with the size of each family and sort by 'Family size' in descending order and then by 'Protein
data['Family size'] = data['Protein families'].map(family_sizes)
data = data.sort_values(by=['Family size', 'Protein families'], ascending=[False, True])
data.drop(columns='Family size', inplace=True) # Drop the 'Family size' column as it is no longer needed
data
Protein families
Protein kinase superfamily 164
Protein kinase superfamily, CMGC Ser/Thr protein kinase family, CDC2/CDKX subfamily 96
Protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily 78
Protein kinase superfamily, Tyr protein kinase family, Insulin receptor subfamily 73
Protein kinase superfamily, CAMK Ser/Thr protein kinase family 56
...
GHMP kinase family, Mevalonate kinase subfamily 1
Protein kinase superfamily, TKL Ser/Thr protein kinase family, ROCO subfamily 1
Glutamate 5-kinase family; Gamma-glutamyl phosphate reductase family 1
Guanylate kinase family 1
GHMP kinase family 1
Length: 126, dtype: int64
Protein
Entry Binding site Active site Sequen
families

ACT_SITE
Protein BINDING 144..152; 278;
359 Q504Y2 kinase /ligand="ATP"; /note="Proton MRRRRAAVAAGFCASFLLGSVLNVLFAPGSEPPRPGQSPEPSPAPG
superfamily /ligand_id="C... acceptor";
/eviden...

Protein BINDING 233..241;

414 Q8IWB6 kinase /ligand="ATP"; NaN MSRAVRLPVPCPVQLGTLRNDSLEAQLHEYVKQGNYVKVKKILKKG
superfamily /ligand_id="C...

Protein BINDING 209..217;

427 Q8NB16 kinase /ligand="ATP"; NaN MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQ
superfamily /ligand_id="C...

Protein BINDING 71;

778 A0A7P0T838 kinase /ligand="ATP"; NaN MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG
superfamily /ligand_id="ChEBI:C...

Protein BINDING 71;

779 A0A7P0T952 kinase /ligand="ATP"; NaN MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG
superfamily /ligand_id="ChEBI:C...

... ... ... ... ...

Protein
kinase BINDING 358;
1770 M1VPF4 superfamily, /ligand="ATP"; NaN MMEAIKKKMQMLKLDKENALDRAEQAEAEQKQAEERSKQLEDELAA
Tyr protein /ligand_id="ChEBI:...
kinase...

ACT_SITE
BINDING 12; 235;
Pyridoxine
21 O00764 /ligand="pyridoxal"; /note="Proton MEEECRVLSIQSHVIRGYVGNRAATFPLQVLGFEIDAVNSVQFSNH
kinase family
/ligand_id="C... acceptor";
/eviden...

SLC34A
transporter
BINDING 906;
family;
1017 M1V485 /ligand="ATP"; NaN MAPWPELGDAQPNPDKYLEGAAGQQPTAPDKSKETNKTDNTEAPVT
Protein
/ligand_id="ChEBI:...
kinase
supe...

ACT_SITE 98;
BINDING 26..33;
Thymidine /note="Proton
82 P04183 /ligand="ATP"; MSCINLPTVLPGSPSKTRGQIQVILGPMFSGKSTELMRRVRRFQIA
kinase family acceptor";
/ligand_id="ChE...
/evidenc...

Type II
pantothenate
BINDING 196;
kinase
542 Q9NVE7 /ligand="acetyl-CoA"; NaN MAECGASGSGSSGDSLDKSITLPPDEIFRNLENAKRFAIDIGGSLT
family;
/ligand_id=...
Damage-
con...

1406 rows × 5 columns

Now let's make the binding and active sites information clearer:

# Extract the location from the binding and active site columns
def extract_location(site_info):
if pd.isnull(site_info):
return None
locations = []
for info in site_info.split(';'):
if 'BINDING' in info or 'ACT_SITE' in info:
locations.append(info.split()[1])
return '; '.join(locations)

# Apply the function to the 'Binding site' and 'Active site' columns to extract the locations
data['Binding site'] = data['Binding site'].apply(extract_location)
data['Active site'] = data['Active site'].apply(extract_location)

# Display the first few rows of the modified dataframe

data.head()

Binding Active
Entry Protein families Sequence
site site

Protein kinase 144..152;

359 Q504Y2 278 MRRRRAAVAAGFCASFLLGSVLNVLFAPGSEPPRPGQSPEPSPAPG...
superfamily 166

Protein kinase 233..241;

414 Q8IWB6 None MSRAVRLPVPCPVQLGTLRNDSLEAQLHEYVKQGNYVKVKKILKKG...
superfamily 273

Protein kinase 209..217;

427 Q8NB16 None MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQ...
superfamily 230

Protein kinase
778 A0A7P0T838 71 None MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG...
superfamily

Protein kinase
779 A0A7P0T952 71 None MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG...
superfamily

# Create a new column that combines the 'Binding site' and 'Active site' columns
data['Binding-Active site'] = data['Binding site'].astype(str) + '; ' + data['Active site'].astype(str)
# Replace 'nan' values with None
data['Binding-Active site'] = data['Binding-Active site'].replace('nan; nan', None)

data.head()

Binding-
Protein Binding Active
Entry Sequence Active
families site site
site

Protein
144..152; 144..152;
359 Q504Y2 kinase 278 MRRRRAAVAAGFCASFLLGSVLNVLFAPGSEPPRPGQSPEPSPAPG...
166 166; 278
superfamily

Protein 233..241;
233..241;
414 Q8IWB6 kinase None MSRAVRLPVPCPVQLGTLRNDSLEAQLHEYVKQGNYVKVKKILKKG... 273;
273
superfamily None

Protein 209..217;
209..217;
427 Q8NB16 kinase None MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQ... 230;
230
superfamily None

Protein
778 A0A7P0T838 kinase 71 None MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG... 71; None
superfamily

Protein
779 A0A7P0T952 kinase 71 None MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG... 71; None
superfamily

Angle bracket symbols in Binding/Active site

In biological databases like UniProt, you may encounter entries in the "Binding site" or "Active site" columns (or any
other feature-related columns) that contain symbols like '<' or '>', these typically indicate positional uncertainty or
boundaries that are outside the range of the sequence currently being annotated:

'<': This symbol is used to indicate that the feature (such as a binding or active site) starts before the position given.
For example, if you see "<5" in the context of a binding site, it suggests that the binding site starts before amino
acid position 5 in the protein sequence.

'>': Conversely, this symbol is used to show that the feature extends beyond the position given. If you see ">200"
for an active site, it implies that the active site extends beyond amino acid position 200.

These annotations provide information about the location of certain functional sites within a protein, but with an
acknowledgment of some level of uncertainty or incompleteness in the data that could be due to various reasons, such
as limitations in experimental data, partial protein sequences, or predictions based on related proteins rather than direct
evidence.

We will filter out entries containing these symbols so as to work with a dataset with certainty on the binding/active sites.
# Find entries containing '<' or '>'
entries_angles = data['Binding-Active site'].str.contains('<|>', na=False)
print(f"Number of entries with angle brackets: {entries_angles.sum()}")

# Remove all rows where the "Binding-Active site" column contains '<' or '>'
data = data[~entries_angles]
print(f"Number of remaining rows: {data.shape[0]}")

Number of entries with angle brackets: 0

Number of remaining rows: 1406

Question mark ("?") symbols in Binding/Active site

In biological databases like UniProt, a question mark ("?") in the "Binding site" or "Active site" columns typically
indicates uncertainty or incomplete information regarding the feature in question. It might mean the exact position of
the binding or active site within the protein sequence may not be clearly determined, or it may be a predicted feature
based on computational models or inferred from homologous proteins, but not yet experimentally verified. It can also be
due to conflicting data or interpretations about the presence or characteristics of the site, or the annotation process just
being incomplete.

# Find rows where the "Binding-Active site" column contains the character "?", treating "?" as a literal character
entries_question_mark = data[data['Binding-Active site'].str.contains('\?', na=False, regex=True)]
print(f"Number of entries with angle brackets: {entries_question_mark.shape[0]}")

# Remove all rows containing '?' in the "Binding-Active site" column

data = data.drop(entries_question_mark.index)
print(f"Number of remaining rows: {data.shape[0]}")

Number of entries with angle brackets: 0

Number of remaining rows: 1406

Binding/active sites labels

Now let's define all aminoacids involved in binding/active sites by expanding the ranges to especify all amino acid
indexes that are a binding/active site:

def expand_ranges(s):
"""Expand ranges into a comma-separated string."""
return re.sub(r'(\d+)\.\.(\d+)', lambda m: ', '.join(map(str, range(int(m.group(1)), int(m.group(2))+1))), str(

data['Binding-Active site'] = data['Binding-Active site'].apply(expand_ranges)

print(data.head())

Entry Protein families Binding site Active site \

359 Q504Y2 Protein kinase superfamily 144..152; 166 278
414 Q8IWB6 Protein kinase superfamily 233..241; 273 None
427 Q8NB16 Protein kinase superfamily 209..217; 230 None
778 A0A7P0T838 Protein kinase superfamily 71 None
779 A0A7P0T952 Protein kinase superfamily 71 None

Sequence \
359 MRRRRAAVAAGFCASFLLGSVLNVLFAPGSEPPRPGQSPEPSPAPG...
414 MSRAVRLPVPCPVQLGTLRNDSLEAQLHEYVKQGNYVKVKKILKKG...
427 MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQ...
778 MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG...
779 MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG...

Binding-Active site
359 144, 145, 146, 147, 148, 149, 150, 151, 152; 1...
414 233, 234, 235, 236, 237, 238, 239, 240, 241; 2...
427 209, 210, 211, 212, 213, 214, 215, 216, 217; 2...
778 71; None
779 71; None

You can now convert the binding/active sites information into a binary label: 1s where there is a binding/active site; 0s
where there is not. Retrieve the indices in 'Bindig/active site' column, and set their corresponding positions in the
protein sequence to 1. All other aminoacids of the sequence are set to 0:

def convert_to_binary_list(binding_active_str, sequence_len):

"""Convert a Binding-Active site string to a binary list based on the sequence length."""
binary_list = [0] * sequence_len
# Retrieve the indices in bindig/active sites and set their corresponding positions to 1
if pd.notna(binding_active_str):
indices = [int(x) - 1 for segment in binding_active_str.split(';') for x in segment.split(',') if x.strip()
for idx in indices:
if 0 <= idx < sequence_len: # Ensure the index is within the valid range
binary_list[idx] = 1

return binary_list
# Apply the function to both datasets
data['Binding-Active site'] = data.apply(lambda row: convert_to_binary_list(row['Binding-Active site'], len(row['Sequ
data.head()

Binding-
Protein Binding Active
Entry Sequence Active
families site site
site

[0, 0, 0,
0, 0, 0,
Protein
144..152; 0, 0, 0,
359 Q504Y2 kinase 278 MRRRRAAVAAGFCASFLLGSVLNVLFAPGSEPPRPGQSPEPSPAPG...
166 0, 0, 0,
superfamily
0, 0, 0,
...

[0, 0, 0,
0, 0, 0,
Protein
233..241; 0, 0, 0,
414 Q8IWB6 kinase None MSRAVRLPVPCPVQLGTLRNDSLEAQLHEYVKQGNYVKVKKILKKG...
273 0, 0, 0,
superfamily
0, 0, 0,
...

[0, 0, 0,
0, 0, 0,
Protein
209..217; 0, 0, 0,
427 Q8NB16 kinase None MENLKHIITLGQVIHKRCEEMKYCKKQCRRLGHRVLGLIKPLEMLQ...
230 0, 0, 0,
superfamily
0, 0, 0,
...

[0, 0, 0,
0, 0, 0,
Protein
0, 0, 0,
778 A0A7P0T838 kinase 71 None MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG...
0, 0, 0,
superfamily
0, 0, 0,
...

[0, 0, 0,
0, 0, 0,
Protein
0, 0, 0,
779 A0A7P0T952 kinase 71 None MPRVKAAQAGRQSSAKRHLAEQFAVGEIITDMAKKEWKVGLPIGQG...
0, 0, 0,
superfamily
0, 0, 0,
...

Split train/test sets

Let's create a split of the data into training and test sets based on UniProt protein families, such that it ensures entire
protein families are either in the training set or the test set. The goal is that the test set will contain completely "new"
families of proteins that are not seen in the training set, so the evaluation represents the model's ability to generalize to
entirely new families of proteins that it has not seen during training.

Notably, this is different from the traiditional stratified split, which aims to preserve the distribution of classes across
both sets.

# Get the number of distinct protein families

num_families = data['Protein families'].nunique()
print(f"Number of distinct protein families: {num_families}")

Number of distinct protein families: 126

def split_data_by_family(data, test_ratio=0.20):

"""
Splits the dataset into train and test sets by entire protein families (not a family-stratified split!).

Parameters:
- data: pandas DataFrame containing the dataset with a 'Protein families' column.
- test_ratio: float, the proportion of the dataset to include in the test split.

Returns:
- test_df: pandas DataFrame containing the test set.
- train_df: pandas DataFrame containing the training set.
"""
# Get unique protein families and shuffle them to randomize the selection
unique_families = data['Protein families'].unique()
np.random.shuffle(unique_families)

# Loop through the shuffled families and add rows to the test set
test_rows = []
current_test_rows = 0
for family in unique_families:
family_rows = data[data['Protein families'] == family].index.tolist()
if current_test_rows + len(family_rows) <= int(test_ratio * data.shape[0]):
test_rows.extend(family_rows)
current_test_rows += len(family_rows)
else:
# If adding the current family exceeds the target, stop adding
test_rows.extend(family_rows)
break

# Create the test and train datasets

train_rows = [i for i in data.index if i not in test_rows]
test_df = data.loc[test_rows]
train_df = data.loc[train_rows]

return test_df, train_df

test_df, train_df = split_data_by_family(data, test_ratio=0.20)

print(test_df.shape[0], train_df.shape[0])

392 1014

test_df.head()

Binding
Binding Active
Entry Protein families Sequence Activ
site site

62..67; [0, 0,
89..92; 0, 0,
APS kinase family;
101; 0, 0,
39 O43252 Sulfate None MEIPGSLCKKVKLSNNAQNWGMQRATNVTYQAHHVSRNKRGQVVGT...
106..109; 0, 0,
adenylyltransferase...
132..133; 0, 0,
171; ...

52..57;
[0, 0,
79..82;
0, 0,
APS kinase family; 91;
0, 0,
68 O95340 Sulfate 96..99; None MSGIKKQKTENQQKSTNVVYQAHHVSRNKRGQVVGTRGGFRGCTVW...
0, 0,
adenylyltransferase... 122..123;
0, 0,
161;
174...

[0, 0,
0, 0,
Protein kinase
0, 0,
4 A0A2P9DU05 superfamily, AGC 121 214 MSRPPPTGKMPGAPETAPGDGAGASRQRKLEALIRDPRSPINVESL...
0, 0,
Ser/Thr protei...
0, 0,

[0, 0,
0, 0,
Protein kinase
104..112; 0, 0,
12 O00141 superfamily, AGC 222 MTVKTEAAKGTLTYSRMRGMVAILIAFMKQRRMGLNDFIQKIANNS...
127 0, 0,
Ser/Thr protei...
0, 0,

[0, 0,
0, 0,
Protein kinase
103..111; 0, 0,
22 O14578 superfamily, AGC 221 MLKFKYGARNPLDAGAAEPIASRASRLNLFFQGKPPFMTQQQMSPL...
126 0, 0,
Ser/Thr protei...
0, 0,

In case you don't want to keep the entire train/test datasets, you can create a smaller version (with a random
representation of the original dataset). Uncomment the code below if that is the case:

# # Percentage of data you want to keep

# k = 0.05 # for keeping 5% of the data

# # Generate random indices representing a percentage of each dataset

# train_df = train_df.sample(frac=k, random_state=42)
# test_df = test_df.sample(frac=k, random_state=42)

Split sequences into chunks

Sequences aren’t always of the same length. We will split the longer protein sequences and their lables into non-
overlapping chunks of certain length or less to account for a given context window of ESM-2 models. Most protein
sequences are on average 350 or so residues, so having longer context windows is often unnecessary, but keep in mind
this will effect training time and batch size. Here, we pick a context of 1000.
def split_into_chunks(sequences, labels, chunk_size = 1000):
"""Split sequences and labels into chunks of size "chunk_size" or less."""
new_sequences = []
new_labels = []
for seq, lbl in zip(sequences, labels):
if len(seq) > chunk_size:
# Split the sequence and labels into chunks of size "chunk_size" or less
for i in range(0, len(seq), chunk_size):
new_sequences.append(seq[i:i+chunk_size])
new_labels.append(lbl[i:i+chunk_size])
else:
new_sequences.append(seq)
new_labels.append(lbl)

return new_sequences, new_labels

# Create lists of sequences and labels

test_seq = test_df['Sequence'].tolist()
test_labels = test_df['Binding-Active site'].tolist()
train_seq = train_df['Sequence'].tolist()
train_labels = train_df['Binding-Active site'].tolist()

# Apply the function to create new datasets with chunks of size "chunk_size" or less
chunk_size = 1000
test_seq_chunked, test_labels_chunked = split_into_chunks(test_seq, test_labels)
train_seq_chunked, train_labels_chunked = split_into_chunks(train_seq, train_labels)

The resulting train and test files will be exported to the same path where the input data file was located:

filename = os.path.splitext(os.path.basename(file_path))[0]
dir = os.path.dirname(file_path)

# Paths to save the new chunked pickle files

test_labels_path = os.path.join(dir, filename + "_test_labels_chunked_" + str(chunk_size) + ".pkl")
test_seq_path = os.path.join(dir, filename + "_test_sequences_chunked_" + str(chunk_size) + ".pkl")
train_labels_path = os.path.join(dir, filename + "_train_labels_chunked_" + str(chunk_size) + ".pkl")
train_seq_path = os.path.join(dir, filename + "_train_sequences_chunked_" + str(chunk_size) + ".pkl")

# Save the chunked datasets as new pickle files

with open(test_labels_path, 'wb') as file:
pickle.dump(test_labels_chunked, file)
with open(test_seq_path, 'wb') as file:
pickle.dump(test_seq_chunked, file)
with open(train_labels_path, 'wb') as file:
pickle.dump(train_labels_chunked, file)
with open(train_seq_path, 'wb') as file:
pickle.dump(train_seq_chunked, file)

test_labels_path, test_seq_path, train_labels_path, train_seq_path

('/content/gdrive/MyDrive/ESMbind/data/uniprotkb_data_2024_05_29_test_labels_chunked_1000.pkl',
'/content/gdrive/MyDrive/ESMbind/data/uniprotkb_data_2024_05_29_test_sequences_chunked_1000.pkl',
'/content/gdrive/MyDrive/ESMbind/data/uniprotkb_data_2024_05_29_train_labels_chunked_1000.pkl',
'/content/gdrive/MyDrive/ESMbind/data/uniprotkb_data_2024_05_29_train_sequences_chunked_1000.pkl')

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build.

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The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!

Citing this tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Bioinformatics,
title={UniProt data pre-processing for binding site prediction downstream task},
organization={DeepChem},
author={Gómez de Lope, Elisa},
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/UniProt_Data_Preprocessing_for_

year={2024},
}
Exploring Quantum Chemistry with GDB1k
Most of the tutorials we've walked you through so far have focused on applications to the drug discovery realm, but
DeepChem's tool suite works for molecular design problems generally. In this tutorial, we're going to walk through an
example of how to train a simple molecular machine learning for the task of predicting the atomization energy of a
molecule. (Remember that the atomization energy is the energy required to form 1 mol of gaseous atoms from 1 mol of
the molecule in its standard state under standard conditions).

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

With our setup in place, let's do a few standard imports to get the ball rolling.

import deepchem as dc
from sklearn.ensemble import RandomForestRegressor
from sklearn.kernel_ridge import KernelRidge

The ntext step we want to do is load our dataset. We're using a small dataset we've prepared that's pulled out of the
larger GDB benchmarks. The dataset contains the atomization energies for 1K small molecules.

tasks = ["atomization_energy"]
dataset_file = "../../datasets/gdb1k.sdf"
smiles_field = "smiles"
mol_field = "mol"

We now need a way to transform molecules that is useful for prediction of atomization energy. This representation
draws on foundational work [1] that represents a molecule's 3D electrostatic structure as a 2D matrix

of distances scaled by charges, where the

-th element is represented by the following charge structure.

If you're observing carefully, you might ask, wait doesn't this mean that molecules with different numbers of atoms
generate matrices of different sizes? In practice the trick to get around this is that the matrices are "zero-padded." That
is, if you're making coulomb matrices for a set of molecules, you pick a maximum number of atoms

, make the matrices

and set to zero all the extra entries for this molecule. (There's a couple extra tricks that are done under the hood
beyond this. Check out reference [1] or read the source code in DeepChem!)

DeepChem has a built in featurization class dc.feat.CoulombMatrixEig that can generate these featurizations for
you.

featurizer = dc.feat.CoulombMatrixEig(23, remove_hydrogens=False)

Note that in this case, we set the maximum number of atoms to

. Let's now load our dataset file into DeepChem. As in the previous tutorials, we use a Loader class, in particular
dc.data.SDFLoader to load our .sdf file into DeepChem. The following snippet shows how we do this:

loader = dc.data.SDFLoader(
tasks=["atomization_energy"],
featurizer=featurizer)
dataset = loader.create_dataset(dataset_file)
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
RDKit WARNING: [17:25:11] Warning: molecule is tagged as 3D, but all Z coords are zero
/Users/peastman/workspace/deepchem/deepchem/feat/molecule_featurizers/coulomb_matrices.py:141: RuntimeWarning: d
ivide by zero encountered in true_divide
m = np.outer(z, z) / d

For the purposes of this tutorial, we're going to do a random split of the dataset into training, validation, and test. In
general, this split is weak and will considerably overestimate the accuracy of our models, but for now in this simple
tutorial isn't a bad place to get started.

random_splitter = dc.splits.RandomSplitter()
train_dataset, valid_dataset, test_dataset = random_splitter.train_valid_test_split(dataset)

One issue that Coulomb matrix featurizations have is that the range of entries in the matrix

can be large. The charge

term can range very widely. In general, a wide range of values for inputs can throw off learning for the neural network.
For this, a common fix is to normalize the input values so that they fall into a more standard range. Recall that the
normalization transform applies to each feature

of datapoint

where

and

are the mean and standard deviation of the

-th feature. This transformation enables the learning to proceed smoothly. A second point is that the atomization
energies also fall across a wide range. So we apply an analogous transformation normalization transformation to the
output to scale the energies better. We use DeepChem's transformation API to make this happen:

transformers = [
dc.trans.NormalizationTransformer(transform_X=True, dataset=train_dataset),
dc.trans.NormalizationTransformer(transform_y=True, dataset=train_dataset)]

for dataset in [train_dataset, valid_dataset, test_dataset]:

for transformer in transformers:
dataset = transformer.transform(dataset)

Now that we have the data cleanly transformed, let's do some simple machine learning. We'll start by constructing a
random forest on top of the data. We'll use DeepChem's hyperparameter tuning module to do this.

def rf_model_builder(model_dir, **model_params):

sklearn_model = RandomForestRegressor(**model_params)
return dc.models.SklearnModel(sklearn_model, model_dir)
params_dict = {
"n_estimators": [10, 100],
"max_features": ["auto", "sqrt", "log2", None],
}

metric = dc.metrics.Metric(dc.metrics.mean_absolute_error)
optimizer = dc.hyper.GridHyperparamOpt(rf_model_builder)
best_rf, best_rf_hyperparams, all_rf_results = optimizer.hyperparam_search(
params_dict, train_dataset, valid_dataset, output_transformers=transformers,
metric=metric, use_max=False)
for key, value in all_rf_results.items():
print(f'{key}: {value}')
print('Best hyperparams:', best_rf_hyperparams)

_max_featuresauto_n_estimators_10: 91166.92046422893
_max_featuressqrt_n_estimators_10: 90145.02789928475
_max_featureslog2_n_estimators_10: 85589.77206099383
_max_featuresNone_n_estimators_10: 86870.06019336461
_max_featuresauto_n_estimators_100: 86385.9006447343
_max_featuressqrt_n_estimators_100: 85051.76415912053
_max_featureslog2_n_estimators_100: 86443.79468510246
_max_featuresNone_n_estimators_100: 85464.79840440316
Best hyperparams: (100, 'sqrt')

Let's build one more model, a kernel ridge regression, on top of this raw data.

def krr_model_builder(model_dir, **model_params):

sklearn_model = KernelRidge(**model_params)
return dc.models.SklearnModel(sklearn_model, model_dir)

params_dict = {
"kernel": ["laplacian"],
"alpha": [0.0001],
"gamma": [0.0001]
}

metric = dc.metrics.Metric(dc.metrics.mean_absolute_error)
optimizer = dc.hyper.GridHyperparamOpt(krr_model_builder)
best_krr, best_krr_hyperparams, all_krr_results = optimizer.hyperparam_search(
params_dict, train_dataset, valid_dataset, output_transformers=transformers,
metric=metric, use_max=False)
for key, value in all_krr_results.items():
print(f'{key}: {value}')
print('Best hyperparams:', best_krr_hyperparams)

_alpha_0.000100_gamma_0.000100_kernellaplacian: 94056.64820129865
Best hyperparams: ('laplacian', 0.0001, 0.0001)

Congratulations! Time to join the Community!

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sciences. Join the conversation!

Bibliography:
[1] https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.98.146401
DeepQMC tutorial

Background:
The electrons in a molecule are quantum mechanical in nature, meaning they do not follow classical physical laws.
Quantum mechanics only gives a probability of where the electrons will be found and will not tell exactly where it can be
found. This probability is given by the squared magnitude of a property of molecule system called the wavefunction and
is different in each case of different molecule.

For many purposes, the nuclei of the atoms in a molecule can be considered to be stationary, and then we solve to get
the wavefunction of the electrons. The probabilites when modelled into 3 dimensional space, takes the shape of the
orbitals. Like shown in these images below which is taken via electron microscope.

(From the top left, oribtals in order - 2s,

2p(y),3p(y),2p(x),3d(z^2),3d(x^2-y^2))

Don't worry if you cannot remember or relate to the concept of orbitals, just remember that these are the space where
electrons are found with more probability.

Using these wavefunctions, the electronic structure(a model containing electrons at its most probable positions) of a
system can be obtained which can be used to calculate the energy at ground state. This value, then can be used to
calculate various properties like ionization energy, electron affinity, etc.

The wavefunction of simple one electron systems like hydrogen atom, helium cation can be found easily, but for heavier
atoms and molecules, electron-electron repulsion comes into act and makes it hard to compute the wavefunctions due
to these interactions. Calculating these wavefunctions exactly will need a lot of computing resources and time which
cannot be feasible to get them. Hence, other various different techniques for to approximate the wavefunction have
been introduced, where there is a different tradeoff between speed and accuracy of the solution. One such method is
the variational Monte Carlo which aims to include the effects of electron correlation in the solution without it.

Since Deep learning act as universal function approximators, it can be used to approximate wavefunction as well!! One
such approach is the DNN based Variational Monte Carlo called paulinet. In this tutorial we will be looking into how to
use Paulinet which is a part of an application called DeepQMC.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

Setup:

First, we have download the DeepQMC application

!pip install -U deepqmc[wf,train,cli]

Looking in indexes: https://pypi.org/simple, https://us-python.pkg.dev/colab-wheels/public/simple/

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Successfully installed click-8.1.3 deepqmc-0.3.1 pyscf-2.0.1 toml-0.10.2 tomlkit-0.7.2 uncertainties-3.1.6

The Hydrogen Molecule

In this section, let us look at a simple molecule to compute for. That is the Hydrogen molecule (2 electrons and 2
nucleus containg each 1 proton) and let us try varying the inter-nuclear distance and its effect on the total energy.

Then, we create our own custom 'Molecule dataset', which is the format in which DeepQMC accepts the parameters of
the molecule system. It shoud contain the list of coordinates of each nucleon(coord), the list of number of protons in
each nucleon(charges), the total ionic charge(charge) and the spin.

Since we are testing out each molecule with different distance, we can loop the Molecule with keeping one nuclei at the
origin and varying the other nuclei x-axis position as given below. Also, the coordinates when given should be in the
magnitude of bohr, where one bohr is equal to 0.52917721092 angstroms.

Then the molecule is loaded and given to train. Here we have modified a particular set of parameters in training to get a
solution with reasonable accuracy in short time. Here we have altered n_steps(the number of steps in which electrons
are sampled), batch_size(number of samples in a single step) and the epoch size(number of steps between sampling
from wavefunction).

Now after training the model, we now will evaluate it, which means that the model will be run from first with the weights
and biases of the neural network which one gets after the training. The result of this evaluation is given as \ uncertainity
data type like '3.14±0.01', for the sake of graphing, we ignore the uncertainity and take the principal integer called the
nominal value(i.e 3.14 in previous case). To do this, we use the 'uncertainities' library.

angstroms_to_bohr=1/(0.52917721092)

from deepqmc import train

from deepqmc import evaluate
from deepqmc.wf import PauliNet
from deepqmc import Molecule
from uncertainties import ufloat
import uncertainties

distances = [0.4, 0.5, 0.6, 0.7, 0.9, 1.1, 1.3, 1.5]

energies = []
for distance in distances:
mol = Molecule(
coords=[[0, 0, 0], [distance*angstroms_to_bohr, 0, 0]],
charges=[1, 1],
charge=0,
spin=0,
)
net = PauliNet.from_hf(mol).cuda()
train(net, n_steps=200, batch_size=200, epoch_size=50)
molecule = evaluate(net)
energies.append(uncertainties.nominal_value(molecule['energy']))

converged SCF energy = -0.937361804612381

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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
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converged SCF energy = -1.12727489687867
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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
FutureWarning)
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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
FutureWarning)
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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
FutureWarning)
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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
FutureWarning)
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cated now calls torch.cuda.reset_peak_memory_stats, which resets /all/ peak memory stats.
FutureWarning)
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Let's plot the results and draw some conclusions from it. The results of the evaluation happens to be a dictionary with
key "energy" and contains the values of the type uncertainities and hence uncertainities library has been used to deal
with

import matplotlib.pyplot as plt

import numpy as np

plt.ylabel("Energy")
plt.xlabel("Inter-nuclear distance")

xpoints = np.array([0.4,0.5,0.6,0.7,0.9,1.1,1.3,1.5])
ypoints = np.array(energies)
#nominal value refers to the principal value excluding the error

plt.plot(xpoints, ypoints)
plt.show()

Here we examined the stability of different hypothetical molecule by differing the coordinates of the nucleus of a
molecule. The one with lowest ground state energy is the most stable one. The inter-nuclear distance so lies at
approximately between 0.7 and 0.8 angstroms as it has a visible minima there.

As you can see here, this result has a lot of applications!! If you calculate the ground state energy for the hydrogen
molecule cation (H2+), then difference in their energy gives you the ionization energy, same can be done if you
calculate the hyrogen moleculet anion to calculate the electron affinity, all from doing simulations!! Also, via this
method, molecular electronic structure can also be determined, which can be used to examine various properties like
conductivity, optical and chemical nature. So, this helps in finding better materials for specific applications.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Introduction to Bioinformatics
So far in this tutorial, we've primarily worked on the problems of cheminformatics. We've been interested in seeing how
we can use the techniques of machine learning to make predictions about the properties of molecules. In this tutorial,
we're going to shift a bit and see how we can use classical computer science techniques and machine learning to tackle
problems in bioinformatics.

For this, we're going to use the venerable biopython library to do some basic bioinformatics. A lot of the material in this
notebook is adapted from the extensive official [Biopython tutorial]http://biopython.org/DIST/docs/tutorial/Tutorial.html).
We strongly recommend checking out the official tutorial after you work through this notebook!

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

Setup
To run DeepChem within Colab, you'll need to run the following cell of installation commands. This will take about 5
minutes to run to completion and install your environment.

!curl -Lo conda_installer.py https://raw.githubusercontent.com/deepchem/deepchem/master/scripts/colab_install.py

import conda_installer
conda_installer.install()
!/root/miniconda/bin/conda info -e

% Total % Received % Xferd Average Speed Time Time Time Current

Dload Upload Total Spent Left Speed
100 3457 100 3457 0 0 11516 0 --:--:-- --:--:-- --:--:-- 11523
add /root/miniconda/lib/python3.10/site-packages to PYTHONPATH
INFO:conda_installer:add /root/miniconda/lib/python3.10/site-packages to PYTHONPATH
python version: 3.10.12
INFO:conda_installer:python version: 3.10.12
fetching installer from https://repo.continuum.io/miniconda/Miniconda3-latest-Linux-x86_64.sh
INFO:conda_installer:fetching installer from https://repo.continuum.io/miniconda/Miniconda3-latest-Linux-x86_64.
sh
done
INFO:conda_installer:done
installing miniconda to /root/miniconda
INFO:conda_installer:installing miniconda to /root/miniconda
done
INFO:conda_installer:done
installing openmm, pdbfixer
INFO:conda_installer:installing openmm, pdbfixer
added conda-forge to channels
INFO:conda_installer:added conda-forge to channels
done
INFO:conda_installer:done
conda packages installation finished!
INFO:conda_installer:conda packages installation finished!
# conda environments:
#
base /root/miniconda

!pip install --pre deepchem

import deepchem
deepchem.__version__
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Installing collected packages: rdkit, deepchem
Successfully installed deepchem-2.7.2.dev20230730200710 rdkit-2023.3.2
WARNING:deepchem.feat.molecule_featurizers.rdkit_descriptors:No normalization for AvgIpc. Feature removed!
WARNING:deepchem.models.torch_models:Skipped loading modules with pytorch-geometric dependency, missing a depend
ency. No module named 'torch_geometric'
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sformers'
WARNING:deepchem.models:cannot import name 'HuggingFaceModel' from 'deepchem.models.torch_models' (/usr/local/li
b/python3.10/dist-packages/deepchem/models/torch_models/__init__.py)
WARNING:deepchem.models:Skipped loading modules with pytorch-geometric dependency, missing a dependency. cannot
import name 'DMPNN' from 'deepchem.models.torch_models' (/usr/local/lib/python3.10/dist-packages/deepchem/models
/torch_models/__init__.py)
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le named 'pytorch_lightning'
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'2.7.2.dev'

We'll use pip to install biopython

!pip install biopython

Collecting biopython
Downloading biopython-1.81-cp310-cp310-manylinux_2_17_x86_64.manylinux2014_x86_64.whl (3.1 MB)
━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━━ 3.1/3.1 MB 12.1 MB/s eta 0:00:00
Requirement already satisfied: numpy in /usr/local/lib/python3.10/dist-packages (from biopython) (1.22.4)
Installing collected packages: biopython
Successfully installed biopython-1.81

import Bio
Bio.__version__

'1.81'

from Bio.Seq import Seq

my_seq = Seq("AGTACACATTG")
my_seq

Seq('AGTACACATTG')

The complement() method in Biopython's Seq object returns the complement of a DNA sequence. It replaces each base
with its complement according to the Watson-Crick base pairing rules. Adenine (A) is complemented by thymine (T), and
guanine (G) is complemented by cytosine (C).

The reverse_complement() method in Biopython's Seq object returns the reverse complement of a DNA sequence. It first
reverses the sequence and then replaces each base with its complement according to the Watson-Crick base pairing
rules.

But why is direction important? Many cellular processes occur only along a particular direction. To understand what
gives a sense of directionality to a strand of DNA, take a look at the pictures below. Carbon atoms in the backbone of
DNA are numbered from 1' to 5' (usually pronounced as "5 prime") in a clockwise direction. One might notice that the
strand on the left has the 5' carbon above the 3' carbon in every nucleotide, resulting in a strand starting with a 5' end
and ending with a 3' end. The strand on the right runs from the 3' end to the 5' end. As hinted earlier, reading of a DNA
strand during replication and transcription only occurs from the 3' end to the 5' end.
my_seq.complement()

Seq('TCATGTGTAAC')

my_seq.reverse_complement()

Seq('CAATGTGTACT')

Parsing Sequence Records

We're going to download a sample fasta file from the Biopython tutorial to use in some exercises. This file is a set of
hits for a sequence (of lady slipper orcid genes).It is basically the DNA sequences of a subfamily of plants belonging to
Orchids(a diverse group of flowering plants) encoding the ribosomal RNA(rRNA).

!wget https://raw.githubusercontent.com/biopython/biopython/master/Doc/examples/ls_orchid.fasta

--2023-08-02 14:46:07-- https://raw.githubusercontent.com/biopython/biopython/master/Doc/examples/ls_orchid.fas

ta
Resolving raw.githubusercontent.com (raw.githubusercontent.com)... 185.199.110.133, 185.199.111.133, 185.199.108
.133, ...
Connecting to raw.githubusercontent.com (raw.githubusercontent.com)|185.199.110.133|:443... connected.
HTTP request sent, awaiting response... 200 OK
Length: 76480 (75K) [text/plain]
Saving to: ‘ls_orchid.fasta’

ls_orchid.fasta 0%[ ] 0 --.-KB/s

ls_orchid.fasta 100%[===================>] 74.69K --.-KB/s in 0.01s

2023-08-02 14:46:07 (5.24 MB/s) - ‘ls_orchid.fasta’ saved [76480/76480]

Let's take a look at what the contents of this file look like:

1. List item
2. List item

from Bio import SeqIO

for seq_record in SeqIO.parse('ls_orchid.fasta', 'fasta'):
print(seq_record.id)
print(repr(seq_record.seq))
print(len(seq_record))

gi|2765658|emb|Z78533.1|CIZ78533
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGATGAGACCGTGG...CGC')
740
gi|2765657|emb|Z78532.1|CCZ78532
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAACAG...GGC')
753
gi|2765656|emb|Z78531.1|CFZ78531
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGCAG...TAA')
748
gi|2765655|emb|Z78530.1|CMZ78530
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAAACAACAT...CAT')
744
gi|2765654|emb|Z78529.1|CLZ78529
Seq('ACGGCGAGCTGCCGAAGGACATTGTTGAGACAGCAGAATATACGATTGAGTGAA...AAA')
733
gi|2765652|emb|Z78527.1|CYZ78527
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGTAG...CCC')
718
gi|2765651|emb|Z78526.1|CGZ78526
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGTAG...TGT')
730
gi|2765650|emb|Z78525.1|CAZ78525
Seq('TGTTGAGATAGCAGAATATACATCGAGTGAATCCGGAGGACCTGTGGTTATTCG...GCA')
704
gi|2765649|emb|Z78524.1|CFZ78524
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATAGTAG...AGC')
740
gi|2765648|emb|Z78523.1|CHZ78523
Seq('CGTAACCAGGTTTCCGTAGGTGAACCTGCGGCAGGATCATTGTTGAGACAGCAG...AAG')
709
gi|2765647|emb|Z78522.1|CMZ78522
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGCAG...GAG')
700
gi|2765646|emb|Z78521.1|CCZ78521
Seq('GTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGTAGAATATATGATCGAGT...ACC')
726
gi|2765645|emb|Z78520.1|CSZ78520
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGCAG...TTT')
753
gi|2765644|emb|Z78519.1|CPZ78519
Seq('ATATGATCGAGTGAATCTGGTGGACTTGTGGTTACTCAGCTCGCCATAGGCTTT...TTA')
699
gi|2765643|emb|Z78518.1|CRZ78518
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGGAGGATCATTGTTGAGATAGTAG...TCC')
658
gi|2765642|emb|Z78517.1|CFZ78517
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGTAG...AGC')
752
gi|2765641|emb|Z78516.1|CPZ78516
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACAGTAT...TAA')
726
gi|2765640|emb|Z78515.1|MXZ78515
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGCTGAGACCGTAG...AGC')
765
gi|2765639|emb|Z78514.1|PSZ78514
Seq('CGTAACAAGGTTTCCGTAGGTGGACCTTCGGGAGGATCATTTTTGAAGCCCCCA...CTA')
755
gi|2765638|emb|Z78513.1|PBZ78513
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCGCCA...GAG')
742
gi|2765637|emb|Z78512.1|PWZ78512
Seq('CGTAACAAGGTTTCCGTAGGTGGACCTTCGGGAGGATCATTTTTGAAGCCCCCA...AGC')
762
gi|2765636|emb|Z78511.1|PEZ78511
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTTCGGAAGGATCATTGTTGAGACCCCCA...GGA')
745
gi|2765635|emb|Z78510.1|PCZ78510
Seq('CTAACCAGGGTTCCGAGGTGACCTTCGGGAGGATTCCTTTTTAAGCCCCCGAAA...TTA')
750
gi|2765634|emb|Z78509.1|PPZ78509
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCGCCA...GGA')
731
gi|2765633|emb|Z78508.1|PLZ78508
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCGCCA...TGA')
741
gi|2765632|emb|Z78507.1|PLZ78507
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCCCCA...TGA')
740
gi|2765631|emb|Z78506.1|PLZ78506
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCGCAA...TGA')
727
gi|2765630|emb|Z78505.1|PSZ78505
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCGCCA...TTT')
711
gi|2765629|emb|Z78504.1|PKZ78504
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTTCGGAAGGATCATTGTTGAGACCGCAA...TAA')
743
gi|2765628|emb|Z78503.1|PCZ78503
Seq('CGTAACCAGGTTTCCGTAGGTGAACCTCCGGAAGGATCCTTGTTGAGACCGCCA...TAA')
727
gi|2765627|emb|Z78502.1|PBZ78502
Seq('CGTAACCAGGTTTCCGTAGGTGAACCTCCGGAAGGATCATTGTTGAGACCGCCA...CGC')
757
gi|2765626|emb|Z78501.1|PCZ78501
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGACCGCAA...AGA')
770
gi|2765625|emb|Z78500.1|PWZ78500
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGCTCATTGTTGAGACCGCAA...AAG')
767
gi|2765624|emb|Z78499.1|PMZ78499
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAGGGATCATTGTTGAGATCGCAT...ACC')
759
gi|2765623|emb|Z78498.1|PMZ78498
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAAGGTCATTGTTGAGATCACAT...AGC')
750
gi|2765622|emb|Z78497.1|PDZ78497
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGC')
788
gi|2765621|emb|Z78496.1|PAZ78496
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCGCAT...AGC')
774
gi|2765620|emb|Z78495.1|PEZ78495
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTCCGGAAGGATCATTGTTGAGATCACAT...GTG')
789
gi|2765619|emb|Z78494.1|PNZ78494
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGGTCGCAT...AAG')
688
gi|2765618|emb|Z78493.1|PGZ78493
Seq('CGTAACAAGGATTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCGCAT...CCC')
719
gi|2765617|emb|Z78492.1|PBZ78492
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCGCAT...ATA')
743
gi|2765616|emb|Z78491.1|PCZ78491
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCGCAT...AGC')
737
gi|2765615|emb|Z78490.1|PFZ78490
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGA')
728
gi|2765614|emb|Z78489.1|PDZ78489
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GGC')
740
gi|2765613|emb|Z78488.1|PTZ78488
Seq('CTGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACGCAATAATTGATCGA...GCT')
696
gi|2765612|emb|Z78487.1|PHZ78487
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TAA')
732
gi|2765611|emb|Z78486.1|PBZ78486
Seq('CGTCACGAGGTTTCCGTAGGTGAATCTGCGGGAGGATCATTGTTGAGATCACAT...TGA')
731
gi|2765610|emb|Z78485.1|PHZ78485
Seq('CTGAACCTGGTGTCCGAAGGTGAATCTGCGGATGGATCATTGTTGAGATATCAT...GTA')
735
gi|2765609|emb|Z78484.1|PCZ78484
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGGGGAAGGATCATTGTTGAGATCACAT...TTT')
720
gi|2765608|emb|Z78483.1|PVZ78483
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GCA')
740
gi|2765607|emb|Z78482.1|PEZ78482
Seq('TCTACTGCAGTGACCGAGATTTGCCATCGAGCCTCCTGGGAGCTTTCTTGCTGG...GCA')
629
gi|2765606|emb|Z78481.1|PIZ78481
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGA')
572
gi|2765605|emb|Z78480.1|PGZ78480
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGA')
587
gi|2765604|emb|Z78479.1|PPZ78479
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGT')
700
gi|2765603|emb|Z78478.1|PVZ78478
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTCCGGAAGGATCAGTGTTGAGATCACAT...GGC')
636
gi|2765602|emb|Z78477.1|PVZ78477
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGC')
716
gi|2765601|emb|Z78476.1|PGZ78476
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...CCC')
592
gi|2765600|emb|Z78475.1|PSZ78475
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GGT')
716
gi|2765599|emb|Z78474.1|PKZ78474
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACGT...CTT')
733
gi|2765598|emb|Z78473.1|PSZ78473
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGG')
626
gi|2765597|emb|Z78472.1|PLZ78472
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGC')
737
gi|2765596|emb|Z78471.1|PDZ78471
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGC')
740
gi|2765595|emb|Z78470.1|PPZ78470
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GTT')
574
gi|2765594|emb|Z78469.1|PHZ78469
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GTT')
594
gi|2765593|emb|Z78468.1|PAZ78468
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCGCAT...GTT')
610
gi|2765592|emb|Z78467.1|PSZ78467
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGA')
730
gi|2765591|emb|Z78466.1|PPZ78466
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...CCC')
641
gi|2765590|emb|Z78465.1|PRZ78465
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGC')
702
gi|2765589|emb|Z78464.1|PGZ78464
Seq('CGTAACAAGGTTTCCGTAGGTGAGCGGAAGGGTCATTGTTGAGATCACATAATA...AGC')
733
gi|2765588|emb|Z78463.1|PGZ78463
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGTTCATTGTTGAGATCACAT...AGC')
738
gi|2765587|emb|Z78462.1|PSZ78462
Seq('CGTCACGAGGTCTCCGGATGTGACCCTGCGGAAGGATCATTGTTGAGATCACAT...CAT')
736
gi|2765586|emb|Z78461.1|PWZ78461
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTCCGGAAGGATCATTGTTGAGATCACAT...TAA')
732
gi|2765585|emb|Z78460.1|PCZ78460
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTCCGGAAGGATCATTGTTGAGATCACAT...TTA')
745
gi|2765584|emb|Z78459.1|PDZ78459
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TTT')
744
gi|2765583|emb|Z78458.1|PHZ78458
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TTG')
738
gi|2765582|emb|Z78457.1|PCZ78457
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTCCGGAAGGATCATTGTTGAGATCACAT...GAG')
739
gi|2765581|emb|Z78456.1|PTZ78456
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGC')
740
gi|2765580|emb|Z78455.1|PJZ78455
Seq('CGTAACCAGGTTTCCGTAGGTGGACCTTCGGGAGGATCATTTTTGAGATCACAT...GCA')
745
gi|2765579|emb|Z78454.1|PFZ78454
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AAC')
695
gi|2765578|emb|Z78453.1|PSZ78453
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GCA')
745
gi|2765577|emb|Z78452.1|PBZ78452
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...GCA')
743
gi|2765576|emb|Z78451.1|PHZ78451
Seq('CGTAACAAGGTTTCCGTAGGTGTACCTCCGGAAGGATCATTGTTGAGATCACAT...AGC')
730
gi|2765575|emb|Z78450.1|PPZ78450
Seq('GGAAGGATCATTGCTGATATCACATAATAATTGATCGAGTTAAGCTGGAGGATC...GAG')
706
gi|2765574|emb|Z78449.1|PMZ78449
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGC')
744
gi|2765573|emb|Z78448.1|PAZ78448
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGG')
742
gi|2765572|emb|Z78447.1|PVZ78447
Seq('CGTAACAAGGATTCCGTAGGTGAACCTGCGGGAGGATCATTGTTGAGATCACAT...AGC')
694
gi|2765571|emb|Z78446.1|PAZ78446
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTCCGGAAGGATCATTGTTGAGATCACAT...CCC')
712
gi|2765570|emb|Z78445.1|PUZ78445
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...TGT')
715
gi|2765569|emb|Z78444.1|PAZ78444
Seq('CGTAACAAGGTTTCCGTAGGGTGAACTGCGGAAGGATCATTGTTGAGATCACAT...ATT')
688
gi|2765568|emb|Z78443.1|PLZ78443
Seq('CGTAACAAGGTTTCCGTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACAT...AGG')
784
gi|2765567|emb|Z78442.1|PBZ78442
Seq('GTAGGTGAACCTGCGGAAGGATCATTGTTGAGATCACATAATAATTGATCGAGT...AGT')
721
gi|2765566|emb|Z78441.1|PSZ78441
Seq('GGAAGGTCATTGCCGATATCACATAATAATTGATCGAGTTAATCTGGAGGATCT...GAG')
703
gi|2765565|emb|Z78440.1|PPZ78440
Seq('CGTAACAAGGTTTCCGTAGGTGGACCTCCGGGAGGATCATTGTTGAGATCACAT...GCA')
744
gi|2765564|emb|Z78439.1|PBZ78439
Seq('CATTGTTGAGATCACATAATAATTGATCGAGTTAATCTGGAGGATCTGTTTACT...GCC')
592

Sequence Objects
A large part of the biopython infrastructure deals with tools for handling sequences. These could be DNA sequences,
RNA sequences, amino acid sequences or even more exotic constructs. Generally, 'Seq' object can be treated like a
normal python string.

from Bio.Seq import Seq

my_seq = Seq("ACAGTAGAC")
print(my_seq)
my_seq

ACAGTAGAC
Seq('ACAGTAGAC')

If we want to code a protein sequence, we can do that just as easily.

my_prot = Seq("AAAAA")
my_prot

Seq('AAAAA')

We can take the length of sequences and index into them like strings.

print(len(my_prot))

my_prot[0]

'A'

You can also use slice notation on sequences to get subsequences.

my_prot[0:3]

Seq('AAA')

You can concatenate sequences if they have the same type so this works.

my_prot + my_prot

Seq('AAAAAAAAAA')

Biopython automatically handles the concatenation as both sequences are of the generic alphabet.

my_prot + my_seq

Seq('AAAAAACAGTAGAC')

Transcription
Transcription is the process by which a DNA sequence is converted into messenger RNA. Remember that this is part of
the "central dogma" of biology in which DNA engenders messenger RNA which engenders proteins. Here's a nice
representation of this cycle borrowed from a Khan academy lesson.

Note from the image above that DNA has two strands. The top strand is typically called the coding strand, and the
bottom the template strand. The template strand is used for the actual transcription process of conversion into
messenger RNA, but in bioinformatics, it's more common to work with the coding strand because this strand has the
same sequence as the RNA transcript (except that RNA has uracil (U) instead of thymine (T)). Let's now see how we can
execute a transcription computationally using Biopython.

from Bio.Seq import Seq

coding_dna = Seq("ATGATCTCGTAA")
print(coding_dna)

ATGATCTCGTAA

template_dna = coding_dna.reverse_complement()
template_dna

Seq('TTACGAGATCAT')

Note that these sequences match those in the image below. You might be confused about why the template_dna
sequence is shown reversed. The reason is that by convention, the template strand is read in the reverse direction.

Let's now see how we can transcribe our coding_dna strand into messenger RNA. This will only swap 'T' for 'U' and
change the alphabet for our object.

messenger_rna = coding_dna.transcribe()
messenger_rna

Seq('AUGAUCUCGUAA')

We can also perform a "back-transcription" to recover the original coding strand from the messenger RNA.

messenger_rna.back_transcribe()

Seq('ATGATCTCGTAA')

Translation
Translation is the next step in the process, whereby a messenger RNA is transformed into a protein sequence. Here's a
beautiful diagram from Wikipedia#/media/File:Ribosome_mRNA_translation_en.svg) that lays out the basics of this
process.
Note how 3 nucleotides at a time correspond to one new amino acid added to the growing protein chain. A set of 3
nucleotides which codes for a given amino acid is called a "codon." We can use the translate() method on the
messenger rna to perform this transformation in code.

messenger_rna.translate()

The translation can also be performed directly from the coding sequence DNA

coding_dna.translate()

Seq('MIS*')

Let's now consider a longer genetic sequence that has some more interesting structure for us to look at.

coding_dna = Seq("ATGGCCATTGTAATGGGCCGCTGAAAGGGTGCCCGATAG")
coding_dna.translate()

Seq('MAIVMGR*KGAR*')

In both of the sequences above, '*' represents the stop codon. A stop codon is a sequence of 3 nucleotides that turns off
the protein machinery. In DNA, the stop codons are 'TGA', 'TAA', 'TAG'. Note that this latest sequence has multiple stop
codons. It's possible to run the machinery up to the first stop codon and pause too.

coding_dna.translate(to_stop=True)

Seq('MAIVMGR')

We're going to introduce a bit of terminology here. A complete coding sequence CDS is a nucleotide sequence of
messenger RNA which is made of a whole number of codons (that is, the length of the sequence is a multiple of 3),
starts with a "start codon" and ends with a "stop codon". A start codon is basically the opposite of a stop codon and is
mostly commonly the sequence "AUG", but can be different (especially if you're dealing with something like bacterial
DNA).

Let's see how we can translate a complete CDS of bacterial messenger RNA.

from Bio.Seq import Seq

gene = Seq(
"GTGAAAAAGATGCAATCTATCGTACTCGCACTTTCCCTGGTTCTGGTCGCTCCCATGGCA"
"GCACAGGCTGCGGAAATTACGTTAGTCCCGTCAGTAAAATTACAGATAGGCGATCGTGAT"
"AATCGTGGCTATTACTGGGATGGAGGTCACTGGCGCGACCACGGCTGGTGGAAACAACAT"
"TATGAATGGCGAGGCAATCGCTGGCACCTACACGGACCGCCGCCACCGCCGCGCCACCAT"
"AAGAAAGCTCCTCATGATCATCACGGCGGTCATGGTCCAGGCAAACATCACCGCTAA"
)
protein_sequence = gene.translate(table="Bacterial")
print(protein_sequence)

VKKMQSIVLALSLVLVAPMAAQAAEITLVPSVKLQIGDRDNRGYYWDGGHWRDHGWWKQHYEWRGNRWHLHGPPPPPRHHKKAPHDHHGGHGPGKHHR*

gene.translate(table="Bacterial", to_stop=True)

Seq('VKKMQSIVLALSLVLVAPMAAQAAEITLVPSVKLQIGDRDNRGYYWDGGHWRDH...HHR')

Handling Annotated Sequences

Sometimes it will be useful for us to be able to handle annotated sequences where there's richer annotations, as in
GenBank or EMBL files. For these purposes, we'll want to use the SeqRecord class.

from Bio.SeqRecord import SeqRecord

help(SeqRecord)

Help on class SeqRecord in module Bio.SeqRecord:

class SeqRecord(builtins.object)
| SeqRecord(seq, id='<unknown id>', name='<unknown name>', description='<unknown description>', dbxrefs=None,
features=None, annotations=None, letter_annotations=None)
|
| A SeqRecord object holds a sequence and information about it.
|
| Main attributes:
| - id - Identifier such as a locus tag (string)
| - seq - The sequence itself (Seq object or similar)
|
| Additional attributes:
| - name - Sequence name, e.g. gene name (string)
| - description - Additional text (string)
| - dbxrefs - List of database cross references (list of strings)
| - features - Any (sub)features defined (list of SeqFeature objects)
| - annotations - Further information about the whole sequence (dictionary).
| Most entries are strings, or lists of strings.
| - letter_annotations - Per letter/symbol annotation (restricted
| dictionary). This holds Python sequences (lists, strings
| or tuples) whose length matches that of the sequence.
| A typical use would be to hold a list of integers
| representing sequencing quality scores, or a string
| representing the secondary structure.
|
| You will typically use Bio.SeqIO to read in sequences from files as
| SeqRecord objects. However, you may want to create your own SeqRecord
| objects directly (see the __init__ method for further details):
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> record = SeqRecord(Seq("MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF"),
| ... id="YP_025292.1", name="HokC",
| ... description="toxic membrane protein")
| >>> print(record)
| ID: YP_025292.1
| Name: HokC
| Description: toxic membrane protein
| Number of features: 0
| Seq('MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF')
|
| If you want to save SeqRecord objects to a sequence file, use Bio.SeqIO
| for this. For the special case where you want the SeqRecord turned into
| a string in a particular file format there is a format method which uses
| Bio.SeqIO internally:
|
| >>> print(record.format("fasta"))
| >YP_025292.1 toxic membrane protein
| MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF
| <BLANKLINE>
|
| You can also do things like slicing a SeqRecord, checking its length, etc
|
| >>> len(record)
| 44
| >>> edited = record[:10] + record[11:]
| >>> print(edited.seq)
| MKQHKAMIVAIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF
| >>> print(record.seq)
| MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF
|
| Methods defined here:
|
| __add__(self, other)
| Add another sequence or string to this sequence.
|
| The other sequence can be a SeqRecord object, a Seq object (or
| similar, e.g. a MutableSeq) or a plain Python string. If you add
| a plain string or a Seq (like) object, the new SeqRecord will simply
| have this appended to the existing data. However, any per letter
| annotation will be lost:
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Quality/solexa_faked.fastq", "fastq-solexa")
| >>> print("%s %s" % (record.id, record.seq))
| slxa_0001_1_0001_01 ACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNN
| >>> print(list(record.letter_annotations))
| ['solexa_quality']
|
| >>> new = record + "ACT"
| >>> print("%s %s" % (new.id, new.seq))
| slxa_0001_1_0001_01 ACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNNACT
| >>> print(list(new.letter_annotations))
| []
|
| The new record will attempt to combine the annotation, but for any
| ambiguities (e.g. different names) it defaults to omitting that
| annotation.
|
| >>> from Bio import SeqIO
| >>> with open("GenBank/pBAD30.gb") as handle:
| ... plasmid = SeqIO.read(handle, "gb")
| >>> print("%s %i" % (plasmid.id, len(plasmid)))
| pBAD30 4923
|
| Now let's cut the plasmid into two pieces, and join them back up the
| other way round (i.e. shift the starting point on this plasmid, have
| a look at the annotated features in the original file to see why this
| particular split point might make sense):
|
| >>> left = plasmid[:3765]
| >>> right = plasmid[3765:]
| >>> new = right + left
| >>> print("%s %i" % (new.id, len(new)))
| pBAD30 4923
| >>> str(new.seq) == str(right.seq + left.seq)
| True
| >>> len(new.features) == len(left.features) + len(right.features)
| True
|
| When we add the left and right SeqRecord objects, their annotation
| is all consistent, so it is all conserved in the new SeqRecord:
|
| >>> new.id == left.id == right.id == plasmid.id
| True
| >>> new.name == left.name == right.name == plasmid.name
| True
| >>> new.description == plasmid.description
| True
| >>> new.annotations == left.annotations == right.annotations
| True
| >>> new.letter_annotations == plasmid.letter_annotations
| True
| >>> new.dbxrefs == left.dbxrefs == right.dbxrefs
| True
|
| However, we should point out that when we sliced the SeqRecord,
| any annotations dictionary or dbxrefs list entries were lost.
| You can explicitly copy them like this:
|
| >>> new.annotations = plasmid.annotations.copy()
| >>> new.dbxrefs = plasmid.dbxrefs[:]
|
| __bool__(self)
| Boolean value of an instance of this class (True).
|
| This behaviour is for backwards compatibility, since until the
| __len__ method was added, a SeqRecord always evaluated as True.
|
| Note that in comparison, a Seq object will evaluate to False if it
| has a zero length sequence.
|
| WARNING: The SeqRecord may in future evaluate to False when its
| sequence is of zero length (in order to better match the Seq
| object behaviour)!
|
| __bytes__(self)
|
| __contains__(self, char)
| Implement the 'in' keyword, searches the sequence.
|
| e.g.
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Fasta/sweetpea.nu", "fasta")
| >>> "GAATTC" in record
| False
| >>> "AAA" in record
| True
|
| This essentially acts as a proxy for using "in" on the sequence:
|
| >>> "GAATTC" in record.seq
| False
| >>> "AAA" in record.seq
| True
|
| Note that you can also use Seq objects as the query,
|
| >>> from Bio.Seq import Seq
| >>> Seq("AAA") in record
| True
|
| See also the Seq object's __contains__ method.
|
| __eq__(self, other)
| Define the equal-to operand (not implemented).
|
| __format__(self, format_spec)
| Return the record as a string in the specified file format.
|
| This method supports the Python format() function and f-strings.
| The format_spec should be a lower case string supported by
| Bio.SeqIO as a text output file format. Requesting a binary file
| format raises a ValueError. e.g.
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> record = SeqRecord(Seq("MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF"),
| ... id="YP_025292.1", name="HokC",
| ... description="toxic membrane protein")
| ...
| >>> format(record, "fasta")
| '>YP_025292.1 toxic membrane protein\nMKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF\n'
| >>> print(f"Here is {record.id} in FASTA format:\n{record:fasta}")
| Here is YP_025292.1 in FASTA format:
| >YP_025292.1 toxic membrane protein
| MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF
| <BLANKLINE>
|
| See also the SeqRecord's format() method.
|
| __ge__(self, other)
| Define the greater-than-or-equal-to operand (not implemented).
|
| __getitem__(self, index)
| Return a sub-sequence or an individual letter.
|
| Slicing, e.g. my_record[5:10], returns a new SeqRecord for
| that sub-sequence with some annotation preserved as follows:
|
| * The name, id and description are kept as-is.
| * Any per-letter-annotations are sliced to match the requested
| sub-sequence.
| * Unless a stride is used, all those features which fall fully
| within the subsequence are included (with their locations
| adjusted accordingly). If you want to preserve any truncated
| features (e.g. GenBank/EMBL source features), you must
| explicitly add them to the new SeqRecord yourself.
| * With the exception of any molecule type, the annotations
| dictionary and the dbxrefs list are not used for the new
| SeqRecord, as in general they may not apply to the
| subsequence. If you want to preserve them, you must explicitly
| copy them to the new SeqRecord yourself.
|
| Using an integer index, e.g. my_record[5] is shorthand for
| extracting that letter from the sequence, my_record.seq[5].
|
| For example, consider this short protein and its secondary
| structure as encoded by the PDB (e.g. H for alpha helices),
| plus a simple feature for its histidine self phosphorylation
| site:
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> from Bio.SeqFeature import SeqFeature, SimpleLocation
| >>> rec = SeqRecord(Seq("MAAGVKQLADDRTLLMAGVSHDLRTPLTRIRLAT"
| ... "EMMSEQDGYLAESINKDIEECNAIIEQFIDYLR"),
| ... id="1JOY", name="EnvZ",
| ... description="Homodimeric domain of EnvZ from E. coli")
| >>> rec.letter_annotations["secondary_structure"] = " S SSSSSSHHHHHTTTHHHHHHHHHHHHHHHHHHHHHHTHHHHHHHHH
HHHHHHHHHHHHTT "
| >>> rec.features.append(SeqFeature(SimpleLocation(20, 21),
| ... type = "Site"))
|
| Now let's have a quick look at the full record,
|
| >>> print(rec)
| ID: 1JOY
| Name: EnvZ
| Description: Homodimeric domain of EnvZ from E. coli
| Number of features: 1
| Per letter annotation for: secondary_structure
| Seq('MAAGVKQLADDRTLLMAGVSHDLRTPLTRIRLATEMMSEQDGYLAESINKDIEE...YLR')
| >>> rec.letter_annotations["secondary_structure"]
| ' S SSSSSSHHHHHTTTHHHHHHHHHHHHHHHHHHHHHHTHHHHHHHHHHHHHHHHHHHHHTT '
| >>> print(rec.features[0].location)
| [20:21]
|
| Now let's take a sub sequence, here chosen as the first (fractured)
| alpha helix which includes the histidine phosphorylation site:
|
| >>> sub = rec[11:41]
| >>> print(sub)
| ID: 1JOY
| Name: EnvZ
| Description: Homodimeric domain of EnvZ from E. coli
| Number of features: 1
| Per letter annotation for: secondary_structure
| Seq('RTLLMAGVSHDLRTPLTRIRLATEMMSEQD')
| >>> sub.letter_annotations["secondary_structure"]
| 'HHHHHTTTHHHHHHHHHHHHHHHHHHHHHH'
| >>> print(sub.features[0].location)
| [9:10]
|
| You can also of course omit the start or end values, for
| example to get the first ten letters only:
|
| >>> print(rec[:10])
| ID: 1JOY
| Name: EnvZ
| Description: Homodimeric domain of EnvZ from E. coli
| Number of features: 0
| Per letter annotation for: secondary_structure
| Seq('MAAGVKQLAD')
|
| Or for the last ten letters:
|
| >>> print(rec[-10:])
| ID: 1JOY
| Name: EnvZ
| Description: Homodimeric domain of EnvZ from E. coli
| Number of features: 0
| Per letter annotation for: secondary_structure
| Seq('IIEQFIDYLR')
|
| If you omit both, then you get a copy of the original record (although
| lacking the annotations and dbxrefs):
|
| >>> print(rec[:])
| ID: 1JOY
| Name: EnvZ
| Description: Homodimeric domain of EnvZ from E. coli
| Number of features: 1
| Per letter annotation for: secondary_structure
| Seq('MAAGVKQLADDRTLLMAGVSHDLRTPLTRIRLATEMMSEQDGYLAESINKDIEE...YLR')
|
| Finally, indexing with a simple integer is shorthand for pulling out
| that letter from the sequence directly:
|
| >>> rec[5]
| 'K'
| >>> rec.seq[5]
| 'K'
|
| __gt__(self, other)
| Define the greater-than operand (not implemented).
|
| __init__(self, seq, id='<unknown id>', name='<unknown name>', description='<unknown description>', dbxrefs=N
one, features=None, annotations=None, letter_annotations=None)
| Create a SeqRecord.
|
| Arguments:
| - seq - Sequence, required (Seq or MutableSeq)
| - id - Sequence identifier, recommended (string)
| - name - Sequence name, optional (string)
| - description - Sequence description, optional (string)
| - dbxrefs - Database cross references, optional (list of strings)
| - features - Any (sub)features, optional (list of SeqFeature objects)
| - annotations - Dictionary of annotations for the whole sequence
| - letter_annotations - Dictionary of per-letter-annotations, values
| should be strings, list or tuples of the same length as the full
| sequence.
|
| You will typically use Bio.SeqIO to read in sequences from files as
| SeqRecord objects. However, you may want to create your own SeqRecord
| objects directly.
|
| Note that while an id is optional, we strongly recommend you supply a
| unique id string for each record. This is especially important
| if you wish to write your sequences to a file.
|
| You can create a 'blank' SeqRecord object, and then populate the
| attributes later.
|
| __iter__(self)
| Iterate over the letters in the sequence.
|
| For example, using Bio.SeqIO to read in a protein FASTA file:
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Fasta/loveliesbleeding.pro", "fasta")
| >>> for amino in record:
| ... print(amino)
| ... if amino == "L": break
| X
| A
| G
| L
| >>> print(record.seq[3])
| L
|
| This is just a shortcut for iterating over the sequence directly:
|
| >>> for amino in record.seq:
| ... print(amino)
| ... if amino == "L": break
| X
| A
| G
| L
| >>> print(record.seq[3])
| L
|
| Note that this does not facilitate iteration together with any
| per-letter-annotation. However, you can achieve that using the
| python zip function on the record (or its sequence) and the relevant
| per-letter-annotation:
|
| >>> from Bio import SeqIO
| >>> rec = SeqIO.read("Quality/solexa_faked.fastq", "fastq-solexa")
| >>> print("%s %s" % (rec.id, rec.seq))
| slxa_0001_1_0001_01 ACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNN
| >>> print(list(rec.letter_annotations))
| ['solexa_quality']
| >>> for nuc, qual in zip(rec, rec.letter_annotations["solexa_quality"]):
| ... if qual > 35:
| ... print("%s %i" % (nuc, qual))
| A 40
| C 39
| G 38
| T 37
| A 36
|
| You may agree that using zip(rec.seq, ...) is more explicit than using
| zip(rec, ...) as shown above.
|
| __le__(self, other)
| Define the less-than-or-equal-to operand (not implemented).
|
| __len__(self)
| Return the length of the sequence.
|
| For example, using Bio.SeqIO to read in a FASTA nucleotide file:
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Fasta/sweetpea.nu", "fasta")
| >>> len(record)
| 309
| >>> len(record.seq)
| 309
|
| __lt__(self, other)
| Define the less-than operand (not implemented).
|
| __ne__(self, other)
| Define the not-equal-to operand (not implemented).
|
| __radd__(self, other)
| Add another sequence or string to this sequence (from the left).
|
| This method handles adding a Seq object (or similar, e.g. MutableSeq)
| or a plain Python string (on the left) to a SeqRecord (on the right).
| See the __add__ method for more details, but for example:
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Quality/solexa_faked.fastq", "fastq-solexa")
| >>> print("%s %s" % (record.id, record.seq))
| slxa_0001_1_0001_01 ACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNN
| >>> print(list(record.letter_annotations))
| ['solexa_quality']
|
| >>> new = "ACT" + record
| >>> print("%s %s" % (new.id, new.seq))
| slxa_0001_1_0001_01 ACTACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNN
| >>> print(list(new.letter_annotations))
| []
|
| __repr__(self)
| Return a concise summary of the record for debugging (string).
|
| The python built in function repr works by calling the object's __repr__
| method. e.g.
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> rec = SeqRecord(Seq("MASRGVNKVILVGNLGQDPEVRYMPNGGAVANITLATSESWRDKAT"
| ... "GEMKEQTEWHRVVLFGKLAEVASEYLRKGSQVYIEGQLRTRKWTDQ"
| ... "SGQDRYTTEVVVNVGGTMQMLGGRQGGGAPAGGNIGGGQPQGGWGQ"
| ... "PQQPQGGNQFSGGAQSRPQQSAPAAPSNEPPMDFDDDIPF"),
| ... id="NP_418483.1", name="b4059",
| ... description="ssDNA-binding protein",
| ... dbxrefs=["ASAP:13298", "GI:16131885", "GeneID:948570"])
| >>> print(repr(rec))
| SeqRecord(seq=Seq('MASRGVNKVILVGNLGQDPEVRYMPNGGAVANITLATSESWRDKATGEMKEQTE...IPF'), id='NP_418483.1', nam
e='b4059', description='ssDNA-binding protein', dbxrefs=['ASAP:13298', 'GI:16131885', 'GeneID:948570'])
|
| At the python prompt you can also use this shorthand:
|
| >>> rec
| SeqRecord(seq=Seq('MASRGVNKVILVGNLGQDPEVRYMPNGGAVANITLATSESWRDKATGEMKEQTE...IPF'), id='NP_418483.1', nam
e='b4059', description='ssDNA-binding protein', dbxrefs=['ASAP:13298', 'GI:16131885', 'GeneID:948570'])
|
| Note that long sequences are shown truncated. Also note that any
| annotations, letter_annotations and features are not shown (as they
| would lead to a very long string).
|
| __str__(self)
| Return a human readable summary of the record and its annotation (string).
|
| The python built in function str works by calling the object's __str__
| method. e.g.
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> record = SeqRecord(Seq("MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF"),
| ... id="YP_025292.1", name="HokC",
| ... description="toxic membrane protein, small")
| >>> print(str(record))
| ID: YP_025292.1
| Name: HokC
| Description: toxic membrane protein, small
| Number of features: 0
| Seq('MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF')
|
| In this example you don't actually need to call str explicitly, as the
| print command does this automatically:
|
| >>> print(record)
| ID: YP_025292.1
| Name: HokC
| Description: toxic membrane protein, small
| Number of features: 0
| Seq('MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF')
|
| Note that long sequences are shown truncated.
|
| count(self, sub, start=None, end=None)
| Return the number of non-overlapping occurrences of sub in seq[start:end].
|
| Optional arguments start and end are interpreted as in slice notation.
| This method behaves as the count method of Python strings.
|
| format(self, format)
| Return the record as a string in the specified file format.
|
| The format should be a lower case string supported as an output
| format by Bio.SeqIO, which is used to turn the SeqRecord into a
| string. e.g.
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> record = SeqRecord(Seq("MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF"),
| ... id="YP_025292.1", name="HokC",
| ... description="toxic membrane protein")
| >>> record.format("fasta")
| '>YP_025292.1 toxic membrane protein\nMKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF\n'
| >>> print(record.format("fasta"))
| >YP_025292.1 toxic membrane protein
| MKQHKAMIVALIVICITAVVAALVTRKDLCEVHIRTGQTEVAVF
| <BLANKLINE>
|
| The Python print function automatically appends a new line, meaning
| in this example a blank line is shown. If you look at the string
| representation you can see there is a trailing new line (shown as
| slash n) which is important when writing to a file or if
| concatenating multiple sequence strings together.
|
| Note that this method will NOT work on every possible file format
| supported by Bio.SeqIO (e.g. some are for multiple sequences only,
| and binary formats are not supported).
|
| islower(self)
| Return True if all ASCII characters in the record's sequence are lowercase.
|
| If there are no cased characters, the method returns False.
|
| isupper(self)
| Return True if all ASCII characters in the record's sequence are uppercase.
|
| If there are no cased characters, the method returns False.
|
| lower(self)
| Return a copy of the record with a lower case sequence.
|
| All the annotation is preserved unchanged. e.g.
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Fasta/aster.pro", "fasta")
| >>> print(record.format("fasta"))
| >gi|3298468|dbj|BAA31520.1| SAMIPF
| GGHVNPAVTFGAFVGGNITLLRGIVYIIAQLLGSTVACLLLKFVTNDMAVGVFSLSAGVG
| VTNALVFEIVMTFGLVYTVYATAIDPKKGSLGTIAPIAIGFIVGANI
| <BLANKLINE>
| >>> print(record.lower().format("fasta"))
| >gi|3298468|dbj|BAA31520.1| SAMIPF
| gghvnpavtfgafvggnitllrgivyiiaqllgstvaclllkfvtndmavgvfslsagvg
| vtnalvfeivmtfglvytvyataidpkkgslgtiapiaigfivgani
| <BLANKLINE>
|
| To take a more annotation rich example,
|
| >>> from Bio import SeqIO
| >>> old = SeqIO.read("EMBL/TRBG361.embl", "embl")
| >>> len(old.features)
| 3
| >>> new = old.lower()
| >>> len(old.features) == len(new.features)
| True
| >>> old.annotations["organism"] == new.annotations["organism"]
| True
| >>> old.dbxrefs == new.dbxrefs
| True
|
| reverse_complement(self, id=False, name=False, description=False, features=True, annotations=False, letter_a
nnotations=True, dbxrefs=False)
| Return new SeqRecord with reverse complement sequence.
|
| By default the new record does NOT preserve the sequence identifier,
| name, description, general annotation or database cross-references -
| these are unlikely to apply to the reversed sequence.
|
| You can specify the returned record's id, name and description as
| strings, or True to keep that of the parent, or False for a default.
|
| You can specify the returned record's features with a list of
| SeqFeature objects, or True to keep that of the parent, or False to
| omit them. The default is to keep the original features (with the
| strand and locations adjusted).
|
| You can also specify both the returned record's annotations and
| letter_annotations as dictionaries, True to keep that of the parent,
| or False to omit them. The default is to keep the original
| annotations (with the letter annotations reversed).
|
| To show what happens to the pre-letter annotations, consider an
| example Solexa variant FASTQ file with a single entry, which we'll
| read in as a SeqRecord:
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Quality/solexa_faked.fastq", "fastq-solexa")
| >>> print("%s %s" % (record.id, record.seq))
| slxa_0001_1_0001_01 ACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNN
| >>> print(list(record.letter_annotations))
| ['solexa_quality']
| >>> print(record.letter_annotations["solexa_quality"])
| [40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15,
14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0, -1, -2, -3, -4, -5]
|
| Now take the reverse complement, here we explicitly give a new
| identifier (the old identifier with a suffix):
|
| >>> rc_record = record.reverse_complement(id=record.id + "_rc")
| >>> print("%s %s" % (rc_record.id, rc_record.seq))
| slxa_0001_1_0001_01_rc NNNNNNACGTACGTACGTACGTACGTACGTACGTACGTACGTACGT
|
| Notice that the per-letter-annotations have also been reversed,
| although this may not be appropriate for all cases.
|
| >>> print(rc_record.letter_annotations["solexa_quality"])
| [-5, -4, -3, -2, -1, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 2
3, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40]
|
| Now for the features, we need a different example. Parsing a GenBank
| file is probably the easiest way to get an nice example with features
| in it...
|
| >>> from Bio import SeqIO
| >>> with open("GenBank/pBAD30.gb") as handle:
| ... plasmid = SeqIO.read(handle, "gb")
| >>> print("%s %i" % (plasmid.id, len(plasmid)))
| pBAD30 4923
| >>> plasmid.seq
| Seq('GCTAGCGGAGTGTATACTGGCTTACTATGTTGGCACTGATGAGGGTGTCAGTGA...ATG')
| >>> len(plasmid.features)
| 13
|
| Now, let's take the reverse complement of this whole plasmid:
|
| >>> rc_plasmid = plasmid.reverse_complement(id=plasmid.id+"_rc")
| >>> print("%s %i" % (rc_plasmid.id, len(rc_plasmid)))
| pBAD30_rc 4923
| >>> rc_plasmid.seq
| Seq('CATGGGCAAATATTATACGCAAGGCGACAAGGTGCTGATGCCGCTGGCGATTCA...AGC')
| >>> len(rc_plasmid.features)
| 13
|
| Let's compare the first CDS feature - it has gone from being the
| second feature (index 1) to the second last feature (index -2), its
| strand has changed, and the location switched round.
|
| >>> print(plasmid.features[1])
| type: CDS
| location: [1081:1960](-)
| qualifiers:
| Key: label, Value: ['araC']
| Key: note, Value: ['araC regulator of the arabinose BAD promoter']
| Key: vntifkey, Value: ['4']
| <BLANKLINE>
| >>> print(rc_plasmid.features[-2])
| type: CDS
| location: [2963:3842](+)
| qualifiers:
| Key: label, Value: ['araC']
| Key: note, Value: ['araC regulator of the arabinose BAD promoter']
| Key: vntifkey, Value: ['4']
| <BLANKLINE>
|
| You can check this new location, based on the length of the plasmid:
|
| >>> len(plasmid) - 1081
| 3842
| >>> len(plasmid) - 1960
| 2963
|
| Note that if the SeqFeature annotation includes any strand specific
| information (e.g. base changes for a SNP), this information is not
| amended, and would need correction after the reverse complement.
|
| Note trying to reverse complement a protein SeqRecord raises an
| exception:
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> protein_rec = SeqRecord(Seq("MAIVMGR"), id="Test",
| ... annotations={"molecule_type": "protein"})
| >>> protein_rec.reverse_complement()
| Traceback (most recent call last):
| ...
| ValueError: Proteins do not have complements!
|
| If you have RNA without any U bases, it must be annotated as RNA
| otherwise it will be treated as DNA by default with A mapped to T:
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> rna1 = SeqRecord(Seq("ACG"), id="Test")
| >>> rna2 = SeqRecord(Seq("ACG"), id="Test", annotations={"molecule_type": "RNA"})
| >>> print(rna1.reverse_complement(id="RC", description="unk").format("fasta"))
| >RC unk
| CGT
| <BLANKLINE>
| >>> print(rna2.reverse_complement(id="RC", description="RNA").format("fasta"))
| >RC RNA
| CGU
| <BLANKLINE>
|
| Also note you can reverse complement a SeqRecord using a MutableSeq:
|
| >>> from Bio.Seq import MutableSeq
| >>> from Bio.SeqRecord import SeqRecord
| >>> rec = SeqRecord(MutableSeq("ACGT"), id="Test")
| >>> rec.seq[0] = "T"
| >>> print("%s %s" % (rec.id, rec.seq))
| Test TCGT
| >>> rc = rec.reverse_complement(id=True)
| >>> print("%s %s" % (rc.id, rc.seq))
| Test ACGA
|
| translate(self, table='Standard', stop_symbol='*', to_stop=False, cds=False, gap=None, id=False, name=False,
description=False, features=False, annotations=False, letter_annotations=False, dbxrefs=False)
| Return new SeqRecord with translated sequence.
|
| This calls the record's .seq.translate() method (which describes
| the translation related arguments, like table for the genetic code),
|
| By default the new record does NOT preserve the sequence identifier,
| name, description, general annotation or database cross-references -
| these are unlikely to apply to the translated sequence.
|
| You can specify the returned record's id, name and description as
| strings, or True to keep that of the parent, or False for a default.
|
| You can specify the returned record's features with a list of
| SeqFeature objects, or False (default) to omit them.
|
| You can also specify both the returned record's annotations and
| letter_annotations as dictionaries, True to keep that of the parent
| (annotations only), or False (default) to omit them.
|
| e.g. Loading a FASTA gene and translating it,
|
| >>> from Bio import SeqIO
| >>> gene_record = SeqIO.read("Fasta/sweetpea.nu", "fasta")
| >>> print(gene_record.format("fasta"))
| >gi|3176602|gb|U78617.1|LOU78617 Lathyrus odoratus phytochrome A (PHYA) gene, partial cds
| CAGGCTGCGCGGTTTCTATTTATGAAGAACAAGGTCCGTATGATAGTTGATTGTCATGCA
| AAACATGTGAAGGTTCTTCAAGACGAAAAACTCCCATTTGATTTGACTCTGTGCGGTTCG
| ACCTTAAGAGCTCCACATAGTTGCCATTTGCAGTACATGGCTAACATGGATTCAATTGCT
| TCATTGGTTATGGCAGTGGTCGTCAATGACAGCGATGAAGATGGAGATAGCCGTGACGCA
| GTTCTACCACAAAAGAAAAAGAGACTTTGGGGTTTGGTAGTTTGTCATAACACTACTCCG
| AGGTTTGTT
| <BLANKLINE>
|
| And now translating the record, specifying the new ID and description:
|
| >>> protein_record = gene_record.translate(table=11,
| ... id="phya",
| ... description="translation")
| >>> print(protein_record.format("fasta"))
| >phya translation
| QAARFLFMKNKVRMIVDCHAKHVKVLQDEKLPFDLTLCGSTLRAPHSCHLQYMANMDSIA
| SLVMAVVVNDSDEDGDSRDAVLPQKKKRLWGLVVCHNTTPRFV
| <BLANKLINE>
|
| upper(self)
| Return a copy of the record with an upper case sequence.
|
| All the annotation is preserved unchanged. e.g.
|
| >>> from Bio.Seq import Seq
| >>> from Bio.SeqRecord import SeqRecord
| >>> record = SeqRecord(Seq("acgtACGT"), id="Test",
| ... description = "Made up for this example")
| >>> record.letter_annotations["phred_quality"] = [1, 2, 3, 4, 5, 6, 7, 8]
| >>> print(record.upper().format("fastq"))
| @Test Made up for this example
| ACGTACGT
| +
| "#$%&'()
| <BLANKLINE>
|
| Naturally, there is a matching lower method:
|
| >>> print(record.lower().format("fastq"))
| @Test Made up for this example
| acgtacgt
| +
| "#$%&'()
| <BLANKLINE>
|
| ----------------------------------------------------------------------
| Data descriptors defined here:
|
| __dict__
| dictionary for instance variables (if defined)
|
| __weakref__
| list of weak references to the object (if defined)
|
| letter_annotations
| Dictionary of per-letter-annotation for the sequence.
|
| For example, this can hold quality scores used in FASTQ or QUAL files.
| Consider this example using Bio.SeqIO to read in an example Solexa
| variant FASTQ file as a SeqRecord:
|
| >>> from Bio import SeqIO
| >>> record = SeqIO.read("Quality/solexa_faked.fastq", "fastq-solexa")
| >>> print("%s %s" % (record.id, record.seq))
| slxa_0001_1_0001_01 ACGTACGTACGTACGTACGTACGTACGTACGTACGTACGTNNNNNN
| >>> print(list(record.letter_annotations))
| ['solexa_quality']
| >>> print(record.letter_annotations["solexa_quality"])
| [40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15,
14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1, 0, -1, -2, -3, -4, -5]
|
| The letter_annotations get sliced automatically if you slice the
| parent SeqRecord, for example taking the last ten bases:
|
| >>> sub_record = record[-10:]
| >>> print("%s %s" % (sub_record.id, sub_record.seq))
| slxa_0001_1_0001_01 ACGTNNNNNN
| >>> print(sub_record.letter_annotations["solexa_quality"])
| [4, 3, 2, 1, 0, -1, -2, -3, -4, -5]
|
| Any python sequence (i.e. list, tuple or string) can be recorded in
| the SeqRecord's letter_annotations dictionary as long as the length
| matches that of the SeqRecord's sequence. e.g.
|
| >>> len(sub_record.letter_annotations)
| 1
| >>> sub_record.letter_annotations["dummy"] = "abcdefghij"
| >>> len(sub_record.letter_annotations)
| 2
|
| You can delete entries from the letter_annotations dictionary as usual:
|
| >>> del sub_record.letter_annotations["solexa_quality"]
| >>> sub_record.letter_annotations
| {'dummy': 'abcdefghij'}
|
| You can completely clear the dictionary easily as follows:
|
| >>> sub_record.letter_annotations = {}
| >>> sub_record.letter_annotations
| {}
|
| Note that if replacing the record's sequence with a sequence of a
| different length you must first clear the letter_annotations dict.
|
| seq
| The sequence itself, as a Seq or MutableSeq object.
|
| ----------------------------------------------------------------------
| Data and other attributes defined here:
|
| __hash__ = None

Let's write a bit of code involving SeqRecord and see how it comes out looking.

from Bio.SeqRecord import SeqRecord

simple_seq = Seq("GATC")
simple_seq_r = SeqRecord(simple_seq)

simple_seq_r.id = "AC12345"
simple_seq_r.description = "Made up sequence"
print(simple_seq_r.id)
print(simple_seq_r.description)

AC12345
Made up sequence

Let's now see how we can use SeqRecord to parse a large fasta file. We'll pull down a file hosted on the biopython site.

!wget https://raw.githubusercontent.com/biopython/biopython/master/Tests/GenBank/NC_005816.fna

--2023-08-02 14:46:08-- https://raw.githubusercontent.com/biopython/biopython/master/Tests/GenBank/NC_005816.fn

a
Resolving raw.githubusercontent.com (raw.githubusercontent.com)... 185.199.108.133, 185.199.109.133, 185.199.110
.133, ...
Connecting to raw.githubusercontent.com (raw.githubusercontent.com)|185.199.108.133|:443... connected.
HTTP request sent, awaiting response... 200 OK
Length: 9853 (9.6K) [text/plain]
Saving to: ‘NC_005816.fna’

NC_005816.fna 100%[===================>] 9.62K --.-KB/s in 0s

2023-08-02 14:46:08 (78.8 MB/s) - ‘NC_005816.fna’ saved [9853/9853]

from Bio import SeqIO

record = SeqIO.read("NC_005816.fna", "fasta")

record

SeqRecord(seq=Seq('TGTAACGAACGGTGCAATAGTGATCCACACCCAACGCCTGAAATCAGATCCAGG...CTG'), id='gi|45478711|ref|NC_00581
6.1|', name='gi|45478711|ref|NC_005816.1|', description='gi|45478711|ref|NC_005816.1| Yersinia pestis biovar Mi
crotus str. 91001 plasmid pPCP1, complete sequence', dbxrefs=[])

Note how there's a number of annotations attached to the SeqRecord object!

Let's take a closer look.

record.id

'gi|45478711|ref|NC_005816.1|'

record.name

'gi|45478711|ref|NC_005816.1|'

record.description

'gi|45478711|ref|NC_005816.1| Yersinia pestis biovar Microtus str. 91001 plasmid pPCP1, complete sequence'

Let's now look at the same sequence, but downloaded from GenBank. We'll download the hosted file from the biopython
tutorial website as before.

!wget https://raw.githubusercontent.com/biopython/biopython/master/Tests/GenBank/NC_005816.gb

--2023-08-02 14:46:08-- https://raw.githubusercontent.com/biopython/biopython/master/Tests/GenBank/NC_005816.gb

Resolving raw.githubusercontent.com (raw.githubusercontent.com)... 185.199.108.133, 185.199.109.133, 185.199.110
.133, ...
Connecting to raw.githubusercontent.com (raw.githubusercontent.com)|185.199.108.133|:443... connected.
HTTP request sent, awaiting response... 200 OK
Length: 31838 (31K) [text/plain]
Saving to: ‘NC_005816.gb’

NC_005816.gb 100%[===================>] 31.09K --.-KB/s in 0.002s

2023-08-02 14:46:08 (12.7 MB/s) - ‘NC_005816.gb’ saved [31838/31838]

from Bio import SeqIO

record = SeqIO.read("NC_005816.gb", "genbank")

record

SeqRecord(seq=Seq('TGTAACGAACGGTGCAATAGTGATCCACACCCAACGCCTGAAATCAGATCCAGG...CTG'), id='NC_005816.1', name='NC_0

05816', description='Yersinia pestis biovar Microtus str. 91001 plasmid pPCP1, complete sequence', dbxrefs=['Pr
oject:58037'])

SeqIO Objects

.count() Method
The .count() method in Biopython's Seq object behaves similar to the .count() method of Python strings. It returns the
number of non-overlapping occurrences of a specific subsequence within the sequence.

from Bio.Seq import Seq

my_seq = Seq("AGTACACATTG")
count_a = my_seq.count('A')
count_tg = my_seq.count('TG')
print(count_a) # Output: 3
print(count_tg) # Output: 1

4
1

MutableSeq objects
Just like the normal Python string, the Seq object is “read only”, or in Python terminology, immutable. Apart from
wanting the Seq object to act like a string, this is also a useful default since in many biological applications you want to
ensure you are not changing your sequence data: you can convert it into a mutable sequence (a MutableSeq object) and
do pretty much anything you want with it
from Bio.Seq import MutableSeq
mutable_seq = MutableSeq("GCCATTGTAATGGGCCGCTGAAAGGGTGCCCGA")

References: [1]https://www.khanacademy.org/science/ap-biology/gene-expression-and-regulation/transcription-and-rna-
processing/a/overview-of-transcription [2]From DNA to RNA. https://www.ncbi.nlm.nih.gov/books/NBK26887/
Multisequence Alignment (MSA)
Proteins are made up of sequences of amino acids chained together. Their amino acid sequence determines their
structure and function. Finding proteins with similar sequences, or homologous proteins, is very useful in identifying the
structures and functions of newly discovered proteins as well as identifying their ancestry. Below is an example of what
a protein amino acid multisequence alignment may look like, taken from [2].

To understand Multiple Sequence Alignment (MSA), it's helpful to first grasp pairwise sequence alignment. Pairwise
sequence alignment is a hypothesis about how two sequences may have evolved from a common ancestor through
events such as mutation, insertion, and deletion. When a nucleotide is aligned with a gap, it represents an indel event—
either a deletion in one sequence or an insertion in the other. When two different nucleotides are aligned, this is
typically interpreted as a substitution or mutation event introduced in one or both of the lineages since the time they
diverged from one another.If identical nucleotides are aligned, it suggests a conserved region, which may indicate
functional importance and possibly homology—evidence that the sequences share a common ancestor. Pairwise
alignment also provides an optimal alignment of two sequences by strategically introducing gaps, making it useful for
comparing sequences and identifying conserved regions.The alignment is an optimal hypothesis but may not reflect the
actual evolutionary path.

Using profile-sequence comparison instead of just sequence-sequence comparison when constructing multiple sequence
alignment utilizes more information. Sequence profiles are based on frequencies of each of the 20 amino acids at each
position in a sequence. Sequence profiles (or PSSMs) tell us how likely it is that a particular amino acid (or nucleotide in
DNA/RNA sequences) at a specific position is due to conservation rather than random chance.This is achieved through
the use of log-odds scores that compare the observed frequency of an amino acid at a particular position in the multiple
sequence alignment (MSA) to its expected frequency under random conditions (i.e., the background probability).

Here is how the position frequence matrix looks. Sequence profile is constructed through the log odds score of these
frequencies.

A Profile Hidden Markov Model is a probabilistic model that represents the sequence conservation at each position
(including insertions and deletions) and the likelihood of transitioning between different sequence states.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

HH-suite
This tutorial will show you the basics of how to use hh-suite. hh-suite is an open source package for searching protein
sequence alignments for homologous proteins. It is the current state of the art for building highly accurate
multisequence alignments (MSA) from a single sequence or from MSAs.

HH-suite leverages profile HMMs to improve the accuracy of detecting remote homologs (sequences that share a
common ancestor but are highly diverged).

Instead of comparing a single sequence against a database of sequences, it aligns one profile HMM against another
profile HMM.The idea is that by comparing two profile HMMs, it can detect relationships between sequence families that
are not apparent when comparing just sequences. This is particularly useful when dealing with highly diverged proteins
or detecting remote homologs.

Setup
Let's start by importing the deepchem sequence_utils module and downloading a database to compare our query
sequence to.

hh-suite provides a set of HMM databases that will work with the software, which you can find here:
http://wwwuser.gwdg.de/~compbiol/data/hhsuite/databases/hhsuite_dbs

dbCAN is a good one for this tutorial because it is a relatively smaller download.

from deepchem.utils import sequence_utils

%%bash
mkdir hh
cd hh
mkdir databases; cd databases
wget http://wwwuser.gwdg.de/~compbiol/data/hhsuite/databases/hhsuite_dbs/dbCAN-fam-V9.tar.gz
tar xzvf dbCAN-fam-V9.tar.gz
dbCAN-fam-V9_a3m.ffdata
dbCAN-fam-V9_a3m.ffindex
dbCAN-fam-V9_hhm.ffdata
dbCAN-fam-V9_hhm.ffindex
dbCAN-fam-V9_cs219.ffdata
dbCAN-fam-V9_cs219.ffindex
dbCAN-fam-V9.md5sum
--2022-02-11 12:47:57-- http://wwwuser.gwdg.de/~compbiol/data/hhsuite/databases/hhsuite_dbs/dbCAN-fam-V9.tar.gz
Resolving wwwuser.gwdg.de (wwwuser.gwdg.de)... 134.76.10.111
Connecting to wwwuser.gwdg.de (wwwuser.gwdg.de)|134.76.10.111|:80... connected.
HTTP request sent, awaiting response... 200 OK
Length: 25882327 (25M) [application/x-gzip]
Saving to: ‘dbCAN-fam-V9.tar.gz’

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3650K .......... .......... .......... .......... .......... 14% 544K 18s
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3750K .......... .......... .......... .......... .......... 15% 35.8M 17s
3800K .......... .......... .......... .......... .......... 15% 402K 18s
3850K .......... .......... .......... .......... .......... 15% 46.9M 18s
3900K .......... .......... .......... .......... .......... 15% 19.3M 17s
3950K .......... .......... .......... .......... .......... 15% 82.5M 17s
4000K .......... .......... .......... .......... .......... 16% 404K 17s
4050K .......... .......... .......... .......... .......... 16% 43.3M 17s
4100K .......... .......... .......... .......... .......... 16% 17.1M 17s
4150K .......... .......... .......... .......... .......... 16% 81.5M 17s
4200K .......... .......... .......... .......... .......... 16% 398K 17s
4250K .......... .......... .......... .......... .......... 17% 50.2M 17s
4300K .......... .......... .......... .......... .......... 17% 45.0M 17s
4350K .......... .......... .......... .......... .......... 17% 1.48M 17s
4400K .......... .......... .......... .......... .......... 17% 539K 17s
4450K .......... .......... .......... .......... .......... 17% 42.5M 17s
4500K .......... .......... .......... .......... .......... 18% 32.2M 16s
4550K .......... .......... .......... .......... .......... 18% 1.51M 16s
4600K .......... .......... .......... .......... .......... 18% 539K 16s
4650K .......... .......... .......... .......... .......... 18% 36.4M 16s
4700K .......... .......... .......... .......... .......... 18% 34.1M 16s
4750K .......... .......... .......... .......... .......... 18% 440K 16s
4800K .......... .......... .......... .......... .......... 19% 4.12M 16s
4850K .......... .......... .......... .......... .......... 19% 38.7M 16s
4900K .......... .......... .......... .......... .......... 19% 44.3M 16s
4950K .......... .......... .......... .......... .......... 19% 406K 16s
5000K .......... .......... .......... .......... .......... 19% 21.4M 16s
5050K .......... .......... .......... .......... .......... 20% 39.1M 16s
5100K .......... .......... .......... .......... .......... 20% 43.1M 16s
5150K .......... .......... .......... .......... .......... 20% 407K 16s
5200K .......... .......... .......... .......... .......... 20% 13.1M 16s
5250K .......... .......... .......... .......... .......... 20% 43.6M 15s
5300K .......... .......... .......... .......... .......... 21% 62.2M 15s
5350K .......... .......... .......... .......... .......... 21% 399K 16s
5400K .......... .......... .......... .......... .......... 21% 58.5M 15s
5450K .......... .......... .......... .......... .......... 21% 38.1M 15s
5500K .......... .......... .......... .......... .......... 21% 55.0M 15s
5550K .......... .......... .......... .......... .......... 22% 401K 15s
5600K .......... .......... .......... .......... .......... 22% 27.5M 15s
5650K .......... .......... .......... .......... .......... 22% 50.0M 15s
5700K .......... .......... .......... .......... .......... 22% 47.0M 15s
5750K .......... .......... .......... .......... .......... 22% 403K 15s
5800K .......... .......... .......... .......... .......... 23% 21.3M 15s
5850K .......... .......... .......... .......... .......... 23% 29.3M 15s
5900K .......... .......... .......... .......... .......... 23% 59.4M 15s
5950K .......... .......... .......... .......... .......... 23% 406K 15s
6000K .......... .......... .......... .......... .......... 23% 19.4M 15s
6050K .......... .......... .......... .......... .......... 24% 34.9M 15s
6100K .......... .......... .......... .......... .......... 24% 39.6M 14s
6150K .......... .......... .......... .......... .......... 24% 408K 15s
6200K .......... .......... .......... .......... .......... 24% 18.4M 14s
6250K .......... .......... .......... .......... .......... 24% 36.5M 14s
6300K .......... .......... .......... .......... .......... 25% 29.7M 14s
6350K .......... .......... .......... .......... .......... 25% 420K 14s
6400K .......... .......... .......... .......... .......... 25% 9.03M 14s
6450K .......... .......... .......... .......... .......... 25% 26.0M 14s
6500K .......... .......... .......... .......... .......... 25% 37.5M 14s
6550K .......... .......... .......... .......... .......... 26% 453K 14s
6600K .......... .......... .......... .......... .......... 26% 3.58M 14s
6650K .......... .......... .......... .......... .......... 26% 18.8M 14s
6700K .......... .......... .......... .......... .......... 26% 40.3M 14s
6750K .......... .......... .......... .......... .......... 26% 455K 14s
6800K .......... .......... .......... .......... .......... 27% 3.64M 14s
6850K .......... .......... .......... .......... .......... 27% 15.0M 14s
6900K .......... .......... .......... .......... .......... 27% 49.0M 14s
6950K .......... .......... .......... .......... .......... 27% 733K 14s
7000K .......... .......... .......... .......... .......... 27% 896K 14s
7050K .......... .......... .......... .......... .......... 28% 23.0M 13s
7100K .......... .......... .......... .......... .......... 28% 27.6M 13s
7150K .......... .......... .......... .......... .......... 28% 1.59M 13s
7200K .......... .......... .......... .......... .......... 28% 537K 13s
7250K .......... .......... .......... .......... .......... 28% 24.2M 13s
7300K .......... .......... .......... .......... .......... 29% 23.2M 13s
7350K .......... .......... .......... .......... .......... 29% 68.7M 13s
7400K .......... .......... .......... .......... .......... 29% 408K 13s
7450K .......... .......... .......... .......... .......... 29% 29.0M 13s
7500K .......... .......... .......... .......... .......... 29% 13.4M 13s
7550K .......... .......... .......... .......... .......... 30% 46.7M 13s
7600K .......... .......... .......... .......... .......... 30% 413K 13s
7650K .......... .......... .......... .......... .......... 30% 19.8M 13s
7700K .......... .......... .......... .......... .......... 30% 29.5M 13s
7750K .......... .......... .......... .......... .......... 30% 17.0M 13s
7800K .......... .......... .......... .......... .......... 31% 463K 13s
7850K .......... .......... .......... .......... .......... 31% 3.53M 13s
7900K .......... .......... .......... .......... .......... 31% 19.9M 13s
7950K .......... .......... .......... .......... .......... 31% 13.7M 12s
8000K .......... .......... .......... .......... .......... 31% 1.72M 12s
8050K .......... .......... .......... .......... .......... 32% 539K 12s
8100K .......... .......... .......... .......... .......... 32% 13.4M 12s
8150K .......... .......... .......... .......... .......... 32% 21.9M 12s
8200K .......... .......... .......... .......... .......... 32% 43.8M 12s
8250K .......... .......... .......... .......... .......... 32% 415K 12s
8300K .......... .......... .......... .......... .......... 33% 14.1M 12s
8350K .......... .......... .......... .......... .......... 33% 25.5M 12s
8400K .......... .......... .......... .......... .......... 33% 23.7M 12s
8450K .......... .......... .......... .......... .......... 33% 416K 12s
8500K .......... .......... .......... .......... .......... 33% 45.8M 12s
8550K .......... .......... .......... .......... .......... 34% 13.0M 12s
8600K .......... .......... .......... .......... .......... 34% 19.6M 12s
8650K .......... .......... .......... .......... .......... 34% 765K 12s
8700K .......... .......... .......... .......... .......... 34% 895K 12s
8750K .......... .......... .......... .......... .......... 34% 14.2M 12s
8800K .......... .......... .......... .......... .......... 35% 18.2M 12s
8850K .......... .......... .......... .......... .......... 35% 43.9M 12s
8900K .......... .......... .......... .......... .......... 35% 416K 12s
8950K .......... .......... .......... .......... .......... 35% 15.8M 12s
9000K .......... .......... .......... .......... .......... 35% 32.0M 11s
9050K .......... .......... .......... .......... .......... 36% 12.4M 11s
9100K .......... .......... .......... .......... .......... 36% 439K 12s
9150K .......... .......... .......... .......... .......... 36% 7.92M 11s
9200K .......... .......... .......... .......... .......... 36% 14.8M 11s
9250K .......... .......... .......... .......... .......... 36% 11.0M 11s
9300K .......... .......... .......... .......... .......... 36% 1.85M 11s
9350K .......... .......... .......... .......... .......... 37% 537K 11s
9400K .......... .......... .......... .......... .......... 37% 16.8M 11s
9450K .......... .......... .......... .......... .......... 37% 25.4M 11s
9500K .......... .......... .......... .......... .......... 37% 12.7M 11s
9550K .......... .......... .......... .......... .......... 37% 422K 11s
9600K .......... .......... .......... .......... .......... 38% 38.8M 11s
9650K .......... .......... .......... .......... .......... 38% 14.7M 11s
9700K .......... .......... .......... .......... .......... 38% 11.1M 11s
9750K .......... .......... .......... .......... .......... 38% 1.84M 11s
9800K .......... .......... .......... .......... .......... 38% 538K 11s
9850K .......... .......... .......... .......... .......... 39% 15.3M 11s
9900K .......... .......... .......... .......... .......... 39% 31.6M 11s
9950K .......... .......... .......... .......... .......... 39% 12.4M 11s
10000K .......... .......... .......... .......... .......... 39% 422K 11s
10050K .......... .......... .......... .......... .......... 39% 14.1M 11s
10100K .......... .......... .......... .......... .......... 40% 30.8M 11s
10150K .......... .......... .......... .......... .......... 40% 12.6M 10s
10200K .......... .......... .......... .......... .......... 40% 1.84M 10s
10250K .......... .......... .......... .......... .......... 40% 532K 10s
10300K .......... .......... .......... .......... .......... 40% 22.0M 10s
10350K .......... .......... .......... .......... .......... 41% 25.4M 10s
10400K .......... .......... .......... .......... .......... 41% 11.9M 10s
10450K .......... .......... .......... .......... .......... 41% 471K 10s
10500K .......... .......... .......... .......... .......... 41% 3.24M 10s
10550K .......... .......... .......... .......... .......... 41% 17.7M 10s
10600K .......... .......... .......... .......... .......... 42% 13.3M 10s
10650K .......... .......... .......... .......... .......... 42% 1.92M 10s
10700K .......... .......... .......... .......... .......... 42% 532K 10s
10750K .......... .......... .......... .......... .......... 42% 12.6M 10s
10800K .......... .......... .......... .......... .......... 42% 39.9M 10s
10850K .......... .......... .......... .......... .......... 43% 12.8M 10s
10900K .......... .......... .......... .......... .......... 43% 803K 10s
10950K .......... .......... .......... .......... .......... 43% 849K 10s
11000K .......... .......... .......... .......... .......... 43% 23.2M 10s
11050K .......... .......... .......... .......... .......... 43% 22.8M 10s
11100K .......... .......... .......... .......... .......... 44% 11.8M 10s
11150K .......... .......... .......... .......... .......... 44% 431K 10s
11200K .......... .......... .......... .......... .......... 44% 12.4M 10s
11250K .......... .......... .......... .......... .......... 44% 17.2M 10s
11300K .......... .......... .......... .......... .......... 44% 14.0M 9s
11350K .......... .......... .......... .......... .......... 45% 1.87M 9s
11400K .......... .......... .......... .......... .......... 45% 533K 9s
11450K .......... .......... .......... .......... .......... 45% 13.6M 9s
11500K .......... .......... .......... .......... .......... 45% 43.6M 9s
11550K .......... .......... .......... .......... .......... 45% 14.5M 9s
11600K .......... .......... .......... .......... .......... 46% 819K 9s
11650K .......... .......... .......... .......... .......... 46% 839K 9s
11700K .......... .......... .......... .......... .......... 46% 16.7M 9s
11750K .......... .......... .......... .......... .......... 46% 40.2M 9s
11800K .......... .......... .......... .......... .......... 46% 11.6M 9s
11850K .......... .......... .......... .......... .......... 47% 453K 9s
11900K .......... .......... .......... .......... .......... 47% 4.96M 9s
11950K .......... .......... .......... .......... .......... 47% 18.2M 9s
12000K .......... .......... .......... .......... .......... 47% 17.6M 9s
12050K .......... .......... .......... .......... .......... 47% 1.87M 9s
12100K .......... .......... .......... .......... .......... 48% 533K 9s
12150K .......... .......... .......... .......... .......... 48% 11.7M 9s
12200K .......... .......... .......... .......... .......... 48% 35.4M 9s
12250K .......... .......... .......... .......... .......... 48% 15.3M 9s
12300K .......... .......... .......... .......... .......... 48% 1.88M 9s
12350K .......... .......... .......... .......... .......... 49% 533K 9s
12400K .......... .......... .......... .......... .......... 49% 12.8M 9s
12450K .......... .......... .......... .......... .......... 49% 22.3M 9s
12500K .......... .......... .......... .......... .......... 49% 21.2M 8s
12550K .......... .......... .......... .......... .......... 49% 806K 8s
12600K .......... .......... .......... .......... .......... 50% 859K 8s
12650K .......... .......... .......... .......... .......... 50% 15.8M 8s
12700K .......... .......... .......... .......... .......... 50% 14.4M 8s
12750K .......... .......... .......... .......... .......... 50% 21.4M 8s
12800K .......... .......... .......... .......... .......... 50% 484K 8s
12850K .......... .......... .......... .......... .......... 51% 3.11M 8s
12900K .......... .......... .......... .......... .......... 51% 12.4M 8s
12950K .......... .......... .......... .......... .......... 51% 18.9M 8s
13000K .......... .......... .......... .......... .......... 51% 20.2M 8s
13050K .......... .......... .......... .......... .......... 51% 429K 8s
13100K .......... .......... .......... .......... .......... 52% 11.1M 8s
13150K .......... .......... .......... .......... .......... 52% 26.1M 8s
13200K .......... .......... .......... .......... .......... 52% 17.4M 8s
13250K .......... .......... .......... .......... .......... 52% 1.98M 8s
13300K .......... .......... .......... .......... .......... 52% 532K 8s
13350K .......... .......... .......... .......... .......... 53% 8.56M 8s
13400K .......... .......... .......... .......... .......... 53% 18.6M 8s
13450K .......... .......... .......... .......... .......... 53% 37.9M 8s
13500K .......... .......... .......... .......... .......... 53% 1.83M 8s
13550K .......... .......... .......... .......... .......... 53% 518K 8s
13600K .......... .......... .......... .......... .......... 54% 53.3M 8s
13650K .......... .......... .......... .......... .......... 54% 17.0M 8s
13700K .......... .......... .......... .......... .......... 54% 32.4M 8s
13750K .......... .......... .......... .......... .......... 54% 1.88M 7s
13800K .......... .......... .......... .......... .......... 54% 518K 8s
13850K .......... .......... .......... .......... .......... 54% 35.2M 7s
13900K .......... .......... .......... .......... .......... 55% 20.6M 7s
13950K .......... .......... .......... .......... .......... 55% 26.7M 7s
14000K .......... .......... .......... .......... .......... 55% 1.90M 7s
14050K .......... .......... .......... .......... .......... 55% 508K 7s
14100K .......... .......... .......... .......... .......... 55% 111M 7s
14150K .......... .......... .......... .......... .......... 56% 21.6M 7s
14200K .......... .......... .......... .......... .......... 56% 43.4M 7s
14250K .......... .......... .......... .......... .......... 56% 1.90M 7s
14300K .......... .......... .......... .......... .......... 56% 509K 7s
14350K .......... .......... .......... .......... .......... 56% 47.6M 7s
14400K .......... .......... .......... .......... .......... 57% 29.2M 7s
14450K .......... .......... .......... .......... .......... 57% 36.3M 7s
14500K .......... .......... .......... .......... .......... 57% 1.07M 7s
14550K .......... .......... .......... .......... .......... 57% 639K 7s
14600K .......... .......... .......... .......... .......... 57% 19.1M 7s
14650K .......... .......... .......... .......... .......... 58% 113M 7s
14700K .......... .......... .......... .......... .......... 58% 40.6M 7s
14750K .......... .......... .......... .......... .......... 58% 1.08M 7s
14800K .......... .......... .......... .......... .......... 58% 638K 7s
14850K .......... .......... .......... .......... .......... 58% 16.9M 7s
14900K .......... .......... .......... .......... .......... 59% 50.2M 7s
14950K .......... .......... .......... .......... .......... 59% 16.4M 7s
15000K .......... .......... .......... .......... .......... 59% 2.03M 7s
15050K .......... .......... .......... .......... .......... 59% 514K 7s
15100K .......... .......... .......... .......... .......... 59% 18.5M 7s
15150K .......... .......... .......... .......... .......... 60% 38.8M 6s
15200K .......... .......... .......... .......... .......... 60% 12.3M 6s
15250K .......... .......... .......... .......... .......... 60% 2.15M 6s
15300K .......... .......... .......... .......... .......... 60% 528K 6s
15350K .......... .......... .......... .......... .......... 60% 6.73M 6s
15400K .......... .......... .......... .......... .......... 61% 110M 6s
15450K .......... .......... .......... .......... .......... 61% 19.5M 6s
15500K .......... .......... .......... .......... .......... 61% 2.14M 6s
15550K .......... .......... .......... .......... .......... 61% 528K 6s
15600K .......... .......... .......... .......... .......... 61% 6.48M 6s
15650K .......... .......... .......... .......... .......... 62% 51.5M 6s
15700K .......... .......... .......... .......... .......... 62% 114M 6s
15750K .......... .......... .......... .......... .......... 62% 2.36M 6s
15800K .......... .......... .......... .......... .......... 62% 530K 6s
15850K .......... .......... .......... .......... .......... 62% 4.16M 6s
15900K .......... .......... .......... .......... .......... 63% 70.9M 6s
15950K .......... .......... .......... .......... .......... 63% 50.3M 6s
16000K .......... .......... .......... .......... .......... 63% 2.44M 6s
16050K .......... .......... .......... .......... .......... 63% 531K 6s
16100K .......... .......... .......... .......... .......... 63% 4.72M 6s
16150K .......... .......... .......... .......... .......... 64% 20.3M 6s
16200K .......... .......... .......... .......... .......... 64% 28.9M 6s
16250K .......... .......... .......... .......... .......... 64% 54.9M 6s
16300K .......... .......... .......... .......... .......... 64% 476K 6s
16350K .......... .......... .......... .......... .......... 64% 2.72M 6s
16400K .......... .......... .......... .......... .......... 65% 20.8M 6s
16450K .......... .......... .......... .......... .......... 65% 38.4M 6s
16500K .......... .......... .......... .......... .......... 65% 33.5M 5s
16550K .......... .......... .......... .......... .......... 65% 914K 5s
16600K .......... .......... .......... .......... .......... 65% 766K 5s
16650K .......... .......... .......... .......... .......... 66% 9.17M 5s
16700K .......... .......... .......... .......... .......... 66% 70.4M 5s
16750K .......... .......... .......... .......... .......... 66% 18.1M 5s
16800K .......... .......... .......... .......... .......... 66% 2.35M 5s
16850K .......... .......... .......... .......... .......... 66% 513K 5s
16900K .......... .......... .......... .......... .......... 67% 8.14M 5s
16950K .......... .......... .......... .......... .......... 67% 44.1M 5s
17000K .......... .......... .......... .......... .......... 67% 16.1M 5s
17050K .......... .......... .......... .......... .......... 67% 2.90M 5s
17100K .......... .......... .......... .......... .......... 67% 532K 5s
17150K .......... .......... .......... .......... .......... 68% 4.43M 5s
17200K .......... .......... .......... .......... .......... 68% 17.9M 5s
17250K .......... .......... .......... .......... .......... 68% 17.0M 5s
17300K .......... .......... .......... .......... .......... 68% 35.4M 5s
17350K .......... .......... .......... .......... .......... 68% 490K 5s
17400K .......... .......... .......... .......... .......... 69% 2.72M 5s
17450K .......... .......... .......... .......... .......... 69% 14.4M 5s
17500K .......... .......... .......... .......... .......... 69% 35.5M 5s
17550K .......... .......... .......... .......... .......... 69% 16.3M 5s
17600K .......... .......... .......... .......... .......... 69% 967K 5s
17650K .......... .......... .......... .......... .......... 70% 772K 5s
17700K .......... .......... .......... .......... .......... 70% 7.62M 5s
17750K .......... .......... .......... .......... .......... 70% 24.5M 5s
17800K .......... .......... .......... .......... .......... 70% 15.2M 5s
17850K .......... .......... .......... .......... .......... 70% 2.99M 5s
17900K .......... .......... .......... .......... .......... 71% 515K 5s
17950K .......... .......... .......... .......... .......... 71% 5.63M 5s
18000K .......... .......... .......... .......... .......... 71% 16.3M 4s
18050K .......... .......... .......... .......... .......... 71% 59.2M 4s
18100K .......... .......... .......... .......... .......... 71% 15.1M 4s
18150K .......... .......... .......... .......... .......... 72% 499K 4s
18200K .......... .......... .......... .......... .......... 72% 2.69M 4s
18250K .......... .......... .......... .......... .......... 72% 14.5M 4s
18300K .......... .......... .......... .......... .......... 72% 18.4M 4s
18350K .......... .......... .......... .......... .......... 72% 14.8M 4s
18400K .......... .......... .......... .......... .......... 72% 1.39M 4s
18450K .......... .......... .......... .......... .......... 73% 628K 4s
18500K .......... .......... .......... .......... .......... 73% 7.11M 4s
18550K .......... .......... .......... .......... .......... 73% 20.1M 4s
18600K .......... .......... .......... .......... .......... 73% 19.7M 4s
18650K .......... .......... .......... .......... .......... 73% 2.87M 4s
18700K .......... .......... .......... .......... .......... 74% 534K 4s
18750K .......... .......... .......... .......... .......... 74% 5.43M 4s
18800K .......... .......... .......... .......... .......... 74% 11.6M 4s
18850K .......... .......... .......... .......... .......... 74% 22.7M 4s
18900K .......... .......... .......... .......... .......... 74% 13.0M 4s
18950K .......... .......... .......... .......... .......... 75% 998K 4s
19000K .......... .......... .......... .......... .......... 75% 776K 4s
19050K .......... .......... .......... .......... .......... 75% 6.50M 4s
19100K .......... .......... .......... .......... .......... 75% 31.0M 4s
19150K .......... .......... .......... .......... .......... 75% 19.4M 4s
19200K .......... .......... .......... .......... .......... 76% 2.86M 4s
19250K .......... .......... .......... .......... .......... 76% 530K 4s
19300K .......... .......... .......... .......... .......... 76% 4.17M 4s
19350K .......... .......... .......... .......... .......... 76% 22.7M 4s
19400K .......... .......... .......... .......... .......... 76% 32.2M 4s
19450K .......... .......... .......... .......... .......... 77% 12.6M 3s
19500K .......... .......... .......... .......... .......... 77% 555K 3s
19550K .......... .......... .......... .......... .......... 77% 2.00M 3s
19600K .......... .......... .......... .......... .......... 77% 6.86M 3s
19650K .......... .......... .......... .......... .......... 77% 24.7M 3s
19700K .......... .......... .......... .......... .......... 78% 33.6M 3s
19750K .......... .......... .......... .......... .......... 78% 2.84M 3s
19800K .......... .......... .......... .......... .......... 78% 530K 3s
19850K .......... .......... .......... .......... .......... 78% 6.11M 3s
19900K .......... .......... .......... .......... .......... 78% 7.70M 3s
19950K .......... .......... .......... .......... .......... 79% 47.5M 3s
20000K .......... .......... .......... .......... .......... 79% 11.6M 3s
20050K .......... .......... .......... .......... .......... 79% 1024K 3s
20100K .......... .......... .......... .......... .......... 79% 776K 3s
20150K .......... .......... .......... .......... .......... 79% 5.19M 3s
20200K .......... .......... .......... .......... .......... 80% 81.5M 3s
20250K .......... .......... .......... .......... .......... 80% 43.4M 3s
20300K .......... .......... .......... .......... .......... 80% 2.88M 3s
20350K .......... .......... .......... .......... .......... 80% 529K 3s
20400K .......... .......... .......... .......... .......... 80% 6.19M 3s
20450K .......... .......... .......... .......... .......... 81% 6.76M 3s
20500K .......... .......... .......... .......... .......... 81% 58.5M 3s
20550K .......... .......... .......... .......... .......... 81% 12.3M 3s
20600K .......... .......... .......... .......... .......... 81% 1.51M 3s
20650K .......... .......... .......... .......... .......... 81% 619K 3s
20700K .......... .......... .......... .......... .......... 82% 5.38M 3s
20750K .......... .......... .......... .......... .......... 82% 40.0M 3s
20800K .......... .......... .......... .......... .......... 82% 51.5M 3s
20850K .......... .......... .......... .......... .......... 82% 13.3M 3s
20900K .......... .......... .......... .......... .......... 82% 509K 3s
20950K .......... .......... .......... .......... .......... 83% 2.89M 3s
21000K .......... .......... .......... .......... .......... 83% 6.67M 3s
21050K .......... .......... .......... .......... .......... 83% 40.1M 2s
21100K .......... .......... .......... .......... .......... 83% 16.8M 2s
21150K .......... .......... .......... .......... .......... 83% 3.17M 2s
21200K .......... .......... .......... .......... .......... 84% 528K 2s
21250K .......... .......... .......... .......... .......... 84% 6.20M 2s
21300K .......... .......... .......... .......... .......... 84% 8.17M 2s
21350K .......... .......... .......... .......... .......... 84% 17.7M 2s
21400K .......... .......... .......... .......... .......... 84% 24.9M 2s
21450K .......... .......... .......... .......... .......... 85% 1.00M 2s
21500K .......... .......... .......... .......... .......... 85% 771K 2s
21550K .......... .......... .......... .......... .......... 85% 5.64M 2s
21600K .......... .......... .......... .......... .......... 85% 12.3M 2s
21650K .......... .......... .......... .......... .......... 85% 112M 2s
21700K .......... .......... .......... .......... .......... 86% 3.08M 2s
21750K .......... .......... .......... .......... .......... 86% 597K 2s
21800K .......... .......... .......... .......... .......... 86% 2.91M 2s
21850K .......... .......... .......... .......... .......... 86% 6.65M 2s
21900K .......... .......... .......... .......... .......... 86% 12.6M 2s
21950K .......... .......... .......... .......... .......... 87% 53.0M 2s
22000K .......... .......... .......... .......... .......... 87% 3.17M 2s
22050K .......... .......... .......... .......... .......... 87% 531K 2s
22100K .......... .......... .......... .......... .......... 87% 5.84M 2s
22150K .......... .......... .......... .......... .......... 87% 8.21M 2s
22200K .......... .......... .......... .......... .......... 88% 10.0M 2s
22250K .......... .......... .......... .......... .......... 88% 111M 2s
22300K .......... .......... .......... .......... .......... 88% 3.32M 2s
22350K .......... .......... .......... .......... .......... 88% 531K 2s
22400K .......... .......... .......... .......... .......... 88% 4.38M 2s
22450K .......... .......... .......... .......... .......... 89% 17.7M 2s
22500K .......... .......... .......... .......... .......... 89% 10.1M 2s
22550K .......... .......... .......... .......... .......... 89% 29.9M 2s
22600K .......... .......... .......... .......... .......... 89% 1.03M 2s
22650K .......... .......... .......... .......... .......... 89% 779K 2s
22700K .......... .......... .......... .......... .......... 90% 5.55M 1s
22750K .......... .......... .......... .......... .......... 90% 24.9M 1s
22800K .......... .......... .......... .......... .......... 90% 10.3M 1s
22850K .......... .......... .......... .......... .......... 90% 52.2M 1s
22900K .......... .......... .......... .......... .......... 90% 512K 1s
22950K .......... .......... .......... .......... .......... 90% 3.46M 1s
23000K .......... .......... .......... .......... .......... 91% 5.22M 1s
23050K .......... .......... .......... .......... .......... 91% 14.6M 1s
23100K .......... .......... .......... .......... .......... 91% 18.8M 1s
23150K .......... .......... .......... .......... .......... 91% 3.36M 1s
23200K .......... .......... .......... .......... .......... 91% 541K 1s
23250K .......... .......... .......... .......... .......... 92% 5.19M 1s
23300K .......... .......... .......... .......... .......... 92% 8.97M 1s
23350K .......... .......... .......... .......... .......... 92% 12.7M 1s
23400K .......... .......... .......... .......... .......... 92% 13.2M 1s
23450K .......... .......... .......... .......... .......... 92% 3.80M 1s
23500K .......... .......... .......... .......... .......... 93% 540K 1s
23550K .......... .......... .......... .......... .......... 93% 4.97M 1s
23600K .......... .......... .......... .......... .......... 93% 9.17M 1s
23650K .......... .......... .......... .......... .......... 93% 13.6M 1s
23700K .......... .......... .......... .......... .......... 93% 8.62M 1s
23750K .......... .......... .......... .......... .......... 94% 4.47M 1s
23800K .......... .......... .......... .......... .......... 94% 536K 1s
23850K .......... .......... .......... .......... .......... 94% 5.21M 1s
23900K .......... .......... .......... .......... .......... 94% 9.52M 1s
23950K .......... .......... .......... .......... .......... 94% 6.19M 1s
24000K .......... .......... .......... .......... .......... 95% 24.5M 1s
24050K .......... .......... .......... .......... .......... 95% 4.77M 1s
24100K .......... .......... .......... .......... .......... 95% 519K 1s
24150K .......... .......... .......... .......... .......... 95% 8.05M 1s
24200K .......... .......... .......... .......... .......... 95% 8.30M 1s
24250K .......... .......... .......... .......... .......... 96% 6.79M 1s
24300K .......... .......... .......... .......... .......... 96% 14.7M 1s
24350K .......... .......... .......... .......... .......... 96% 1.96M 1s
24400K .......... .......... .......... .......... .......... 96% 621K 0s
24450K .......... .......... .......... .......... .......... 96% 6.38M 0s
24500K .......... .......... .......... .......... .......... 97% 10.8M 0s
24550K .......... .......... .......... .......... .......... 97% 6.81M 0s
24600K .......... .......... .......... .......... .......... 97% 13.8M 0s
24650K .......... .......... .......... .......... .......... 97% 1.18M 0s
24700K .......... .......... .......... .......... .......... 97% 755K 0s
24750K .......... .......... .......... .......... .......... 98% 9.82M 0s
24800K .......... .......... .......... .......... .......... 98% 10.3M 0s
24850K .......... .......... .......... .......... .......... 98% 6.37M 0s
24900K .......... .......... .......... .......... .......... 98% 16.3M 0s
24950K .......... .......... .......... .......... .......... 98% 1.18M 0s
25000K .......... .......... .......... .......... .......... 99% 755K 0s
25050K .......... .......... .......... .......... .......... 99% 10.5M 0s
25100K .......... .......... .......... .......... .......... 99% 9.45M 0s
25150K .......... .......... .......... .......... .......... 99% 6.48M 0s
25200K .......... .......... .......... .......... .......... 99% 15.5M 0s
25250K .......... .......... ..... 100% 3.71M=14s

2022-02-11 12:48:12 (1.72 MB/s) - ‘dbCAN-fam-V9.tar.gz’ saved [25882327/25882327]

Using hhsearch
hhblits and hhsearch are the main functions in hhsuite which identify homologous proteins. They do this by calculating a
profile hidden Markov model (HMM) from a given alignment and searching over a reference HMM proteome database
using the Viterbi algorithm. Then the most similar HMMs are realigned and output to the user. To learn more, check out
the original paper in the references above.

Run a function from hhsuite with no parameters to read its documentation.

!hhsearch
HHsearch 3.3.0
Search a database of HMMs with a query alignment or query HMM
(c) The HH-suite development team
Steinegger M, Meier M, Mirdita M, Vöhringer H, Haunsberger S J, and Söding J (2019)
HH-suite3 for fast remote homology detection and deep protein annotation.
BMC Bioinformatics, doi:10.1186/s12859-019-3019-7

Usage: hhsearch -i query -d database [options]

-i <file> input/query multiple sequence alignment (a2m, a3m, FASTA) or HMM
Options:
-d <name> database name (e.g. uniprot20_29Feb2012)
Multiple databases may be specified with '-d <db1> -d <db2> ...'
-e [0,1] E-value cutoff for inclusion in result alignment (def=0.001)

Input alignment format:

-M a2m use A2M/A3M (default): upper case = Match; lower case = Insert;
'-' = Delete; '.' = gaps aligned to inserts (may be omitted)
-M first use FASTA: columns with residue in 1st sequence are match states
-M [0,100] use FASTA: columns with fewer than X% gaps are match states
-tags/-notags do NOT / do neutralize His-, C-myc-, FLAG-tags, and trypsin
recognition sequence to background distribution (def=-notags)

Output options:
-o <file> write results in standard format to file (default=<infile.hhr>)
-oa3m <file> write result MSA with significant matches in a3m format
-blasttab <name> write result in tabular BLAST format (compatible to -m 8 or -outfmt 6 output)
1 2 3 4 5 6 7 8 9 10 11 12
query target #match/tLen alnLen #mismatch #gapOpen qstart qend tstart tend eval score
-add_cons generate consensus sequence as master sequence of query MSA (default=don't)
-hide_cons don't show consensus sequence in alignments (default=show)
-hide_pred don't show predicted 2ndary structure in alignments (default=show)
-hide_dssp don't show DSSP 2ndary structure in alignments (default=show)
-show_ssconf show confidences for predicted 2ndary structure in alignments
Filter options applied to query MSA, database MSAs, and result MSA
-all show all sequences in result MSA; do not filter result MSA
-id [0,100] maximum pairwise sequence identity (def=90)
-diff [0,inf[ filter MSAs by selecting most diverse set of sequences, keeping
at least this many seqs in each MSA block of length 50
Zero and non-numerical values turn off the filtering. (def=100)
-cov [0,100] minimum coverage with master sequence (%) (def=0)
-qid [0,100] minimum sequence identity with master sequence (%) (def=0)
-qsc [0,100] minimum score per column with master sequence (default=-20.0)
-neff [1,inf] target diversity of multiple sequence alignment (default=off)
-mark do not filter out sequences marked by ">@"in their name line

HMM-HMM alignment options:

-norealign do NOT realign displayed hits with MAC algorithm (def=realign)
-ovlp <int> banded alignment: forbid <ovlp> largest diagonals |i-j| of DP matrix (def=0)
-mact [0,1[ posterior prob threshold for MAC realignment controlling greedi-
ness at alignment ends: 0:global >0.1:local (default=0.35)
-glob/-loc use global/local alignment mode for searching/ranking (def=local)
Other options:
-v <int> verbose mode: 0:no screen output 1:only warnings 2: verbose (def=2)
-cpu <int> number of CPUs to use (for shared memory SMPs) (default=2)

An extended list of options can be obtained by calling 'hhblits -h all'

Example: hhsearch -i a.1.1.1.a3m -d scop70_1.71

Download databases from <http://wwwuser.gwdg.de/~compbiol/data/hhsuite/databases/hhsuite_dbs/>.

- 12:48:13.127 ERROR: Database is missing (see -d)!

Let's do an example. Say we have a protein which we want to compare to a MSA in order to identify any homologous
regions. For this we can use hhsearch.

Now let's take some protein sequence and search through the dbCAN database to see if we can find any potential
homologous regions. First we will specify the sequence and save it as a FASTA file or a3m file in order to be readable by
hhsearch. I pulled this sequence from the example query.a3m in the hhsuite data directory.

with open('protein.fasta', 'w') as f:

f.write("""
>Uncharacterized bovine protein (Fragment)
--PAGGQCtgiWHLLTRPLRP--QGRLPGLRVKYVFLVWLGVFAGSWMAYTHYSSYAELCRGHICQVVICDQFRKGIISGSICQDLCHLHQVEWRTCLSSVPGQQVYSGLWQGKEVT
""")

Then we can call hhsearch, specifying the query sequence with the -i flag, the database to search through with -d, and
the output with -o.

from deepchem.utils import sequence_utils

dataset_path = 'protein.fasta'
data_dir = 'hh/databases'
results = sequence_utils.hhsearch(dataset_path,database='dbCAN-fam-V9', data_dir=data_dir)

- 12:48:13.301 INFO: Search results will be written to /home/tony/github/deepchem/examples/tutorials/protein.hhr

- 12:48:13.331 INFO: /home/tony/github/deepchem/examples/tutorials/protein.fasta is in A2M, A3M or FASTA format

- 12:48:13.331 WARNING: Input alignment /home/tony/github/deepchem/examples/tutorials/protein.fasta looks like a

ligned FASTA instead of A2M/A3M format. Consider using '-M first' or '-M 50'

- 12:48:13.331 INFO: NOTE: Use the '-add_cons' option to calculate a consensus sequence as first sequence of the
alignment with hhconsensus or hhmake.

- 12:48:13.331 INFO: Searching 683 database HHMs without prefiltering

- 12:48:13.332 INFO: Iteration 1

- 12:48:13.420 INFO: Scoring 683 HMMs using HMM-HMM Viterbi alignment

- 12:48:13.460 INFO: Alternative alignment: 0

- 12:48:13.611 INFO: 683 alignments done

- 12:48:13.612 INFO: Alternative alignment: 1

- 12:48:13.625 INFO: 38 alignments done

- 12:48:13.625 INFO: Alternative alignment: 2

- 12:48:13.629 INFO: 3 alignments done

- 12:48:13.629 INFO: Alternative alignment: 3

- 12:48:13.655 INFO: Premerge done

- 12:48:13.656 INFO: Realigning 10 HMM-HMM alignments using Maximum Accuracy algorithm

- 12:48:13.692 INFO: 0 sequences belonging to 0 database HMMs found with an E-value < 0.001

- 12:48:13.692 INFO: Number of effective sequences of resulting query HMM: Neff = 1

#open the results and print them

f = open("protein.hhr", "r")
print(f.read())

Query Uncharacterized bovine protein (Fragment)

Match_columns 431
No_of_seqs 1 out of 1
Neff 1
Searched_HMMs 683
Date Fri Feb 11 12:48:13 2022
Command hhsearch -i /home/tony/github/deepchem/examples/tutorials/protein.fasta -d hh/databases/dbCAN-fam-
V9 -oa3m /home/tony/github/deepchem/examples/tutorials/results.a3m -cpu 4 -e 0.001

No Hit Prob E-value P-value Score SS Cols Query HMM Template HMM
1 ABJ15796.1|231-344|9.6e-33 8.2 2.9 0.0042 25.2 0.0 13 224-236 40-52 (116)
2 lcl|consensus 5.1 5.2 0.0076 17.1 0.0 14 182-195 1-14 (21)
3 ABW08129.1|GT4|GT97||563-891 4.8 5.7 0.0084 26.6 0.0 46 104-150 93-140 (329)
4 AEO62162.1|AA13||19-250 4.6 6 0.0087 25.5 0.0 18 330-347 139-156 (232)
5 BAF49076.1|GH5_26.hmm|8.3e-11| 2.4 13 0.02 21.9 0.0 12 287-298 45-56 (141)
6 BBD44721.1 Hypothetical protei 2.3 14 0.02 25.7 0.0 81 110-221 326-406 (552)
7 AAU92474.1|CBM2|2-82|1.9e-23 2.3 14 0.02 19.1 0.0 19 222-240 13-33 (104)
8 BAX82587.1 hypothetical protei 2.3 14 0.021 25.7 0.0 25 104-128 466-490 (656)
9 AHE46274.1|GH13_13.hmm|1.6e-20 2.0 16 0.024 24.1 0.0 45 143-199 99-143 (393)
10 ACF55060.1|GH13_13.hmm|2.5e-47 1.9 17 0.025 23.2 0.0 22 144-165 74-95 (330)

No 1
>ABJ15796.1|231-344|9.6e-33
Probab=8.16 E-value=2.9 Score=25.22 Aligned_cols=13 Identities=46% Similarity=0.795 Sum_probs=10.2 Templa
te_Neff=3.400

Q Uncharacterize 223 YCGDLYVTEGVPL 235 (430)

Q Consensus 224 ycgdlyvtegvpl 236 (431)
--||||.||||--
T Consensus 40 I~Gnlyi~eGVG~ 52 (116)
T ABJ15796.1|231 40 INGNLYIAEGVGE 52 (116)
Confidence 3599999999853

No 2
>lcl|consensus
Probab=5.13 E-value=5.2 Score=17.13 Aligned_cols=14 Identities=29% Similarity=0.437 Sum_probs=10.2 Templa
te_Neff=4.300
Q Uncharacterize 181 DFNKDNRVSLAEAK 194 (430)
Q Consensus 182 dfnkdnrvslaeak 195 (431)
|.|.|++|+-.++-
T Consensus 1 DvN~DG~Vna~D~~ 14 (21)
T lcl|consensus_ 1 DVNGDGKVNALDLA 14 (21)
Confidence 67888888766553

No 3
>ABW08129.1|GT4|GT97||563-891
Probab=4.78 E-value=5.7 Score=26.58 Aligned_cols=46 Identities=20% Similarity=0.367 Sum_probs=28.5 Templa
te_Neff=1.500

Q Uncharacterize 103 YSGLWQGKEVTIKCGIEESLN--SKAGSDGAPRRELVLFDKPSRGTSIK 149 (430)

Q Consensus 104 ysglwqgkevtikcgieesln--skagsdgaprrelvlfdkpsrgtsik 150 (431)
..|+|. |...+.-.|.-... .+..-|.+|..|-++||-|.||-+-+
T Consensus 93 ~~G~W~-~~~~~~~~i~~~~DheG~r~m~~~~~~~T~i~e~~Rk~~~~~ 140 (329)
T ABW08129.1|GT4 93 FTGKWE-KHFQTSPKIDYRFDHEGKRSMDDVFSEETFIMEFPRKNGIDK 140 (329)
Confidence 457774 33333333433333 45556778888889999988887654

No 4
>AEO62162.1|AA13||19-250
Probab=4.61 E-value=6 Score=25.50 Aligned_cols=18 Identities=39% Similarity=0.936 Sum_probs=14.8 Template
_Neff=1.600

Q Uncharacterize 329 RGRRCEHSADCTYGRDCR 346 (430)

Q Consensus 330 rgrrcehsadctygrdcr 347 (431)
.|..|..|+||+-|..|-
T Consensus 139 ~Gq~C~y~pDC~~gq~C~ 156 (232)
T AEO62162.1|AA1 139 SGQTCGYSPDCSPGQPCW 156 (232)
Confidence 467899999999998774

No 5
>BAF49076.1|GH5_26.hmm|8.3e-11|182-335
Probab=2.39 E-value=13 Score=21.92 Aligned_cols=12 Identities=33% Similarity=0.720 Sum_probs=9.5 Template
_Neff=1.900

Q Uncharacterize 286 HGAYGNFYMCET 297 (430)

Q Consensus 287 hgaygnfymcet 298 (431)
.|+|++|||-..
T Consensus 45 ~G~yn~~Y~l~s 56 (141)
T BAF49076.1|GH5 45 QGTYNGNYMLTS 56 (141)
Confidence 478999998654

No 6
>BBD44721.1 Hypothetical protein PEIBARAKI_4714 [Petrimonas sp. IBARAKI]
Probab=2.34 E-value=14 Score=25.75 Aligned_cols=81 Identities=23% Similarity=0.240 Sum_probs=46.6 Templat
e_Neff=3.400

Q Uncharacterize 109 GKEVTIKCGIEESLNSKAGSDGAPRRELVLFDKPSRGTSIKEFREMTLSFLKANLGDLPSLPALVGRVLLMADFNKDNRV 188 (430

)
Q Consensus 110 gkevtikcgieeslnskagsdgaprrelvlfdkpsrgtsikefremtlsflkanlgdlpslpalvgrvllmadfnkdnrv 189 (431
)
|..|+|-.|+|+..+-+. +++-.-.|+.-+|-+.+++|.+--. .|-+ ||-.+-+
T Consensus 326 g~~V~Iya~l~~~~~~~~-------------~~~~~~~S~~~~Rg~Aa~~L~rGAd----------GIyl---FN~f~~~ 379 (552
)
T BBD44721.1_con 326 GTGVKIYAGLEDARAPDP-------------STRRETNSLEAYRGRAANALSRGAD----------GIYL---FNYFYPP 379 (552
)
Confidence 777888888888744332 4455566888888888888765322 2333 4443332

Q Uncharacterize 189 SLAEAKSVWALLQRNEFLLLLSLQEKEHASRL 220 (430)

Q Consensus 190 slaeaksvwallqrnefllllslqekehasrl 221 (431)
.. --.|||.-.=+-.|.-|+|.|+-..
T Consensus 380 ~~-----~~~llrelgd~~~L~~~~K~y~~s~ 406 (552)
T BBD44721.1_con 380 QM-----RSPLLRELGDLETLATQEKLYALSI 406 (552)
Confidence 11 1233443333445566788876543

No 7
>AAU92474.1|CBM2|2-82|1.9e-23
Probab=2.33 E-value=14 Score=19.07 Aligned_cols=19 Identities=26% Similarity=0.562 Sum_probs=14.3 Templat
e_Neff=6.600

Q Uncharacterize 221 LGYCGDLYVT--EGVPLSSWP 239 (430)

Q Consensus 222 lgycgdlyvt--egvplsswp 240 (431)
-||++++-|+ ...+++.|-
T Consensus 13 ~Gf~~~v~vtN~~~~~i~~W~ 33 (104)
T AAU92474.1|CBM 13 GGFQANVTVTNTGSSAISGWT 33 (104)
Confidence 3789998888 567777774

No 8
>BAX82587.1 hypothetical protein ALGA_4297 [Marinifilaceae bacterium SPP2]
Probab=2.28 E-value=14 Score=25.65 Aligned_cols=25 Identities=40% Similarity=0.314 Sum_probs=21.4 Templat
e_Neff=1.500

Q Uncharacterize 103 YSGLWQGKEVTIKCGIEESLNSKAG 127 (430)

Q Consensus 104 ysglwqgkevtikcgieeslnskag 128 (431)
-+.+||+|.+.||..||.|-|-+--
T Consensus 466 ~kd~~~tk~~sik~kietSenFtl~ 490 (656)
T BAX82587.1_con 466 NKDLNQTKQVSIKTKIETSENFTLS 490 (656)
Confidence 5789999999999999998876543

No 9
>AHE46274.1|GH13_13.hmm|1.6e-201|415-835
Probab=2.04 E-value=16 Score=24.14 Aligned_cols=45 Identities=29% Similarity=0.332 Sum_probs=25.7 Templat
e_Neff=3.900

Q Uncharacterize 142 PSRGTSIKEFREMTLSFLKANLGDLPSLPALVGRVLLMADFNKDNRVSLAEAKSVWA 198 (430)

Q Consensus 143 psrgtsikefremtlsflkanlgdlpslpalvgrvllmadfnkdnrvslaeaksvwa 199 (431)
|.-.+-|+|||+|.-+. -+.=-||.+=.=||--+-.-+ .++||..
T Consensus 99 ~~g~~Ri~EfR~MV~al-----------h~~GlrVv~DVVyNHT~~sg~-~~~SVlD 143 (393)
T AHE46274.1|GH1 99 PDGVARIKEFRAMVQAL-----------HAMGLRVVMDVVYNHTAASGQ-YDNSVLD 143 (393)
Confidence 34445589999998653 222235655555676655544 3345543

No 10
>ACF55060.1|GH13_13.hmm|2.5e-47|336-542
Probab=1.94 E-value=17 Score=23.24 Aligned_cols=22 Identities=23% Similarity=0.371 Sum_probs=17.6 Templat
e_Neff=4.500

Q Uncharacterize 143 SRGTSIKEFREMTLSFLKANLG 164 (430)

Q Consensus 144 srgtsikefremtlsflkanlg 165 (431)
+.-+.|+||++|...+=++.++
T Consensus 74 dp~~RI~E~K~mI~~lH~~GI~ 95 (330)
T ACF55060.1|GH1 74 DPYGRIREFKQMIQALHDAGIR 95 (330)
Confidence 4456799999999988887765

Two files are output and saved to the dataset directory, results.hhr and results.a3m. results.hhr is the hhsuite results
file, which is a summary of the results. results.a3m is the actual MSA file.

In the hhr file, the 'Prob' column describes the estimated probability of the query sequence being at least partially
homologous to the template. Probabilities of 95% or more are nearly certain, and probabilities of 30% or more call for
closer consideration. The E value tells you how many random matches with a better score would be expected if the
searched database was unrelated to the query sequence. These results show that none of the sequences align well with
our randomly chosen protein, which is to be expected because our query sequence was chosen at random.

Now let's check the results if we use a sequence that we know will align with something in the dbCAN database. I pulled
this protein from the dockerin.faa file in dbCAN.

with open('protein2.fasta', 'w') as f:

f.write(""">dockerin,22,NCBI-Bacteria,gi|125972715|ref|YP_001036625.1|,162-245,0.033
SCADLNGDGKITSSDYNLLKRYILHLIDKFPIGNDETDEGINDGFNDETDEDINDSFIEANSKFAFDIFKQISKDEQGKNVFIS
""")

dataset_path = 'protein2.fasta'
sequence_utils.hhsearch(dataset_path,database='dbCAN-fam-V9', data_dir=data_dir)

#open the results and print them

f = open("protein2.hhr", "r")
print(f.read())
- 12:48:13.823 INFO: Search results will be written to /home/tony/github/deepchem/examples/tutorials/protein2.hh
r

- 12:48:13.851 INFO: /home/tony/github/deepchem/examples/tutorials/protein2.fasta is in A2M, A3M or FASTA format

- 12:48:13.852 INFO: Searching 683 database HHMs without prefiltering

- 12:48:13.852 INFO: Iteration 1

- 12:48:13.873 INFO: Scoring 683 HMMs using HMM-HMM Viterbi alignment

- 12:48:13.913 INFO: Alternative alignment: 0

- 12:48:13.979 INFO: 683 alignments done

- 12:48:13.979 INFO: Alternative alignment: 1

- 12:48:13.982 INFO: 10 alignments done

- 12:48:13.982 INFO: Alternative alignment: 2

- 12:48:13.984 INFO: 3 alignments done

- 12:48:13.984 INFO: Alternative alignment: 3

- 12:48:13.986 INFO: 3 alignments done

Query dockerin,22,NCBI-Bacteria,gi|125972715|ref|YP_001036625.1|,162-245,0.033
Match_columns 84
No_of_seqs 1 out of 1
Neff 1
Searched_HMMs 683
Date Fri Feb 11 12:48:14 2022
Command hhsearch -i /home/tony/github/deepchem/examples/tutorials/protein2.fasta -d hh/databases/dbCAN-fam
-V9 -oa3m /home/tony/github/deepchem/examples/tutorials/results.a3m -cpu 4 -e 0.001

No Hit Prob E-value P-value Score SS Cols Query HMM Template HMM
1 lcl|consensus 97.0 5.9E-08 8.7E-11 43.5 0.0 21 4-24 1-21 (21)
2 ABN51673.1|GH124|2-334|2.6e-21 92.5 0.00033 4.8E-07 45.5 0.0 68 1-75 21-88 (318)
3 AAK20911.1|PL11|47-657|0 15.7 1.1 0.0017 27.6 0.0 14 1-14 329-342 (606)
4 AGE62576.1|PL11_1.hmm|0|1-596 10.2 2.1 0.0031 26.0 0.0 13 1-13 118-130 (602)
5 AAZ21803.1|GH103|26-328|1.7e-8 9.3 2.4 0.0035 22.4 0.0 10 4-13 175-184 (293)
6 AGE62576.1|PL11_1.hmm|0|1-596 5.5 4.8 0.007 23.9 0.0 12 1-12 329-340 (602)
7 AAK20911.1|PL11|47-657|0 5.5 4.8 0.007 23.8 0.0 13 1-13 118-130 (606)
8 APU21542.1|PL11_2.hmm|1.4e-162 4.9 5.6 0.0082 23.5 0.0 14 2-15 318-331 (579)
9 AAK20911.1|PL11|47-657|0 4.7 5.8 0.0084 23.4 0.0 10 3-12 184-193 (606)
10 AGE62576.1|PL11_1.hmm|0|1-596 4.6 6 0.0088 23.3 0.0 7 4-10 185-191 (602)

No 1
>lcl|consensus
Probab=97.03 E-value=5.9e-08 Score=43.48 Aligned_cols=21 Identities=57% Similarity=1.061 Sum_probs=20.1 T
emplate_Neff=4.300

Q dockerin,22,NC 4 DLNGDGKITSSDYNLLKRYIL 24 (84)

Q Consensus 4 dlngdgkitssdynllkryil 24 (84)
|+|+||+|+..|+.++|||+|
T Consensus 1 DvN~DG~Vna~D~~~l~~~l~ 21 (21)
T lcl|consensus_ 1 DVNGDGKVNALDLALLKKYLL 21 (21)
Confidence 899999999999999999986

No 2
>ABN51673.1|GH124|2-334|2.6e-219
Probab=92.52 E-value=0.00033 Score=45.54 Aligned_cols=68 Identities=31% Similarity=0.523 Sum_probs=51.6 T
emplate_Neff=1.400

Q dockerin,22,NC 1 SCADLNGDGKITSSDYNLLKRYILHLIDKFPIGNDETDEGINDGFNDETDEDINDSFIEANSKFAFDIFKQISKD 75 (84)

Q Consensus 1 scadlngdgkitssdynllkryilhlidkfpigndetdegindgfndetdedindsfieanskfafdifkqiskd 75 (84)
++||+||||+|+||||+|||| ||++|++||+++|||+|++|.. .-|+|.--.+-.++.....+.+.|.
T Consensus 21 v~GD~n~dgvv~isd~vl~k~-~l~~~a~~~a~~d~w~g~vN~d------d~I~D~d~~~~kryll~mir~~pk~ 88 (318)
T ABN51673.1|GH1 21 VIGDVNADGVVNISDYVLMKR-ILRIIADFPADDDMWVGDVNGD------DVINDIDCNYLKRYLLHMIREFPKN 88 (318)
Confidence 489999999999999999999 9999999999999999999854 3333333333344444444444443

No 3
>AAK20911.1|PL11|47-657|0
Probab=15.69 E-value=1.1 Score=27.56 Aligned_cols=14 Identities=50% Similarity=0.641 Sum_probs=10.4 Templ
ate_Neff=3.500

Q dockerin,22,NC 1 SCADLNGDGKITSS 14 (84)

Q Consensus 1 scadlngdgkitss 14 (84)
|++|+|+||+=.|-
T Consensus 329 svaDVDgDGkDEIi 342 (606)
T AAK20911.1|PL1 329 SVADVDGDGKDEII 342 (606)
Confidence 57889998886553

No 4
>AGE62576.1|PL11_1.hmm|0|1-596
Probab=10.22 E-value=2.1 Score=26.01 Aligned_cols=13 Identities=46% Similarity=0.772 Sum_probs=10.8 Templ
ate_Neff=3.300

Q dockerin,22,NC 1 SCADLNGDGKITS 13 (84)

Q Consensus 1 scadlngdgkits 13 (84)
|+||||+||...|
T Consensus 118 SVGDLDGDG~YEi 130 (602)
T AGE62576.1|PL1 118 SVGDLDGDGEYEI 130 (602)
Confidence 6899999998654

No 5
>AAZ21803.1|GH103|26-328|1.7e-83
Probab=9.26 E-value=2.4 Score=22.41 Aligned_cols=10 Identities=40% Similarity=0.833 Sum_probs=9.2 Templat
e_Neff=5.600

Q dockerin,22,NC 4 DLNGDGKITS 13 (84)

Q Consensus 4 dlngdgkits 13 (84)
|.|+||++++
T Consensus 175 D~DgDG~~Dl 184 (293)
T AAZ21803.1|GH1 175 DFDGDGRRDL 184 (293)
Confidence 8899999997

No 6
>AGE62576.1|PL11_1.hmm|0|1-596
Probab=5.50 E-value=4.8 Score=23.90 Aligned_cols=12 Identities=58% Similarity=0.847 Sum_probs=7.5 Templat
e_Neff=3.300

Q dockerin,22,NC 1 SCADLNGDGKIT 12 (84)

Q Consensus 1 scadlngdgkit 12 (84)
|+||+|+||+=.
T Consensus 329 svaDVDgDG~DE 340 (602)
T AGE62576.1|PL1 329 SVADVDGDGKDE 340 (602)
Confidence 467777777633

No 7
>AAK20911.1|PL11|47-657|0
Probab=5.47 E-value=4.8 Score=23.84 Aligned_cols=13 Identities=46% Similarity=0.772 Sum_probs=10.6 Templa
te_Neff=3.500

Q dockerin,22,NC 1 SCADLNGDGKITS 13 (84)

Q Consensus 1 scadlngdgkits 13 (84)
|+||||+||...+
T Consensus 118 SVGDLDGDG~yEi 130 (606)
T AAK20911.1|PL1 118 SVGDLDGDGEYEI 130 (606)
Confidence 6899999998654

No 8
>APU21542.1|PL11_2.hmm|1.4e-162|44-417
Probab=4.86 E-value=5.6 Score=23.51 Aligned_cols=14 Identities=50% Similarity=0.715 Sum_probs=9.4 Templat
e_Neff=2.600

Q dockerin,22,NC 2 CADLNGDGKITSSD 15 (84)

Q Consensus 2 cadlngdgkitssd 15 (84)
+.|+|+||+=.+++
T Consensus 318 ~~DvD~DG~DEi~~ 331 (579)
T APU21542.1|PL1 318 IVDVDGDGKDEISD 331 (579)
Confidence 45777777766655

No 9
>AAK20911.1|PL11|47-657|0
Probab=4.74 E-value=5.8 Score=23.38 Aligned_cols=10 Identities=50% Similarity=0.896 Sum_probs=5.6 Templat
e_Neff=3.500

Q dockerin,22,NC 3 ADLNGDGKIT 12 (84)

Q Consensus 3 adlngdgkit 12 (84)
-|+|+|||-.
T Consensus 184 yD~DGDGkAE 193 (606)
T AAK20911.1|PL1 184 YDFDGDGKAE 193 (606)
Confidence 3666666543

No 10
>AGE62576.1|PL11_1.hmm|0|1-596
Probab=4.58 E-value=6 Score=23.30 Aligned_cols=7 Identities=71% Similarity=1.426 Sum_probs=0.0 Template_N
eff=3.300

Q dockerin,22,NC 4 DLNGDGK 10 (84)

Q Consensus 4 dlngdgk 10 (84)
|||||||
T Consensus 185 D~DGDGk 191 (602)
T AGE62576.1|PL1 185 DFDGDGK 191 (602)

- 12:48:14.063 INFO: Premerge done

- 12:48:14.063 INFO: Realigning 10 HMM-HMM alignments using Maximum Accuracy algorithm

- 12:48:14.084 INFO: 4 sequences belonging to 4 database HMMs found with an E-value < 0.001

- 12:48:14.084 INFO: Number of effective sequences of resulting query HMM: Neff = 1.39047

As you can see, there are 2 sequences which are a match for our query sequence.

Using hhblits
hhblits works in much the same way as hhsearch, but it is much faster and slightly less sensitive. This would be more
suited to searching very large databases, or producing a MSA with multiple sequences instead of just one. Let's make
use of that by using our query sequence to create an MSA. We could then use that MSA, with its family of proteins, to
search a larger database for potential matches. This will be much more effective than searching a large database with a
single sequence.

We will use the same dbCAN database. I will pull a glycoside hydrolase protein from UnipProt, so it will likely be related
to some proteins in dbCAN, which has carbohydrate-active enzymes.

The option -oa3m will tell hhblits to output an MSA as an a3m file. The -n option specifies the number of iterations. This
is recommended to keep between 1 and 4, we will try 2.

!wget -O protein3.fasta https://www.uniprot.org/uniprot/G8M3C3.fasta

dataset_path = 'protein3.fasta'
sequence_utils.hhblits(dataset_path,database='dbCAN-fam-V9', data_dir=data_dir)

#open the results and print them

f = open("protein3.hhr", "r")
print(f.read())

--2022-02-11 12:48:14-- https://www.uniprot.org/uniprot/G8M3C3.fasta

Resolving www.uniprot.org (www.uniprot.org)... 193.62.193.81
Connecting to www.uniprot.org (www.uniprot.org)|193.62.193.81|:443... connected.
HTTP request sent, awaiting response... 200
Length: 897 [text/plain]
Saving to: ‘protein3.fasta’

protein3.fasta 100%[===================>] 897 --.-KB/s in 0s

2022-02-11 12:48:15 (1.70 GB/s) - ‘protein3.fasta’ saved [897/897]

- 12:48:15.242 WARNING: Ignoring unknown option -n

- 12:48:15.242 WARNING: Ignoring unknown option 2

- 12:48:15.242 INFO: Search results will be written to /home/tony/github/deepchem/examples/tutorials/protein3.hh

- 12:48:15.270 INFO: /home/tony/github/deepchem/examples/tutorials/protein3.fasta is in A2M, A3M or FASTA format

- 12:48:15.271 INFO: Searching 683 database HHMs without prefiltering

- 12:48:15.271 INFO: Iteration 1

- 12:48:15.424 INFO: Scoring 683 HMMs using HMM-HMM Viterbi alignment

- 12:48:15.465 INFO: Alternative alignment: 0

- 12:48:15.658 INFO: 683 alignments done

- 12:48:15.659 INFO: Alternative alignment: 1

- 12:48:15.697 INFO: 92 alignments done

- 12:48:15.697 INFO: Alternative alignment: 2

- 12:48:15.710 INFO: 7 alignments done

- 12:48:15.710 INFO: Alternative alignment: 3

Query tr|G8M3C3|G8M3C3_HUNCD Dockerin-like protein OS=Hungateiclostridium clariflavum (strain DSM 19732

/ NBRC 101661 / EBR45) OX=720554 GN=Clocl_4007 PE=4 SV=1
Match_columns 728
No_of_seqs 1 out of 1
Neff 1
Searched_HMMs 683
Date Fri Feb 11 12:48:16 2022
Command hhsearch -i /home/tony/github/deepchem/examples/tutorials/protein3.fasta -d hh/databases/dbCAN-fam
-V9 -oa3m /home/tony/github/deepchem/examples/tutorials/results.a3m -cpu 4 -n 2 -e 0.001

No Hit Prob E-value P-value Score SS Cols Query HMM Template HMM
1 AAA91086.1|GH48|150-238|4.7e-1 100.0 7E-195 1E-197 1475.1 0.0 608 31-644 1-619 (620)
2 lcl|consensus 91.8 0.00051 7.4E-07 37.5 0.0 20 668-687 1-20 (21)
3 ABN51673.1|GH124|2-334|2.6e-21 52.5 0.096 0.00014 40.1 0.0 66 663-728 19-85 (318)
4 CAR68154.1|GH88|62-388|4.9e-13 10.5 2 0.003 30.7 0.0 43 421-463 181-223 (329)
5 ACY49347.1|GH105|46-385|1.1e-1 6.4 4 0.0058 28.2 0.0 60 324-383 169-228 (329)
6 QGI59602.1|GH16_22|78-291 5.4 4.9 0.0072 27.6 0.0 10 391-400 33-42 (224)
7 QGI59602.1|GH16_22|78-291 5.3 5 0.0073 27.5 0.0 18 581-598 204-221 (224)
8 AQA16748.1|GH5_51.hmm|7.4e-189 4.9 5.5 0.0081 28.6 0.0 37 644-680 253-291 (351)
9 CCF60459.1|GH5_12.hmm|1.2e-238 3.3 9.1 0.013 28.3 0.0 27 357-383 298-324 (541)
10 ACI55886.1|GH25|58-236|2.7e-60 3.0 10 0.015 22.2 0.0 41 594-634 18-61 (174)

No 1
>AAA91086.1|GH48|150-238|4.7e-10
Probab=100.00 E-value=6.7e-195 Score=1475.15 Aligned_cols=608 Identities=60% Similarity=1.105 Sum_probs=60
4.0 Template_Neff=2.700

Q tr|G8M3C3|G8M3 31 FKDRFNYMYNKIHDPANGYFDSEGIPYHSVETLCVEAPDYGHESTSEAASYYAWLEAVNGKLNGKWSGLTEAWNVVEKYF 110 (728

)
Q Consensus 31 fkdrfnymynkihdpangyfdsegipyhsvetlcveapdyghestseaasyyawleavngklngkwsglteawnvvekyf 110 (728
)
|.||||+||+|||||+|||||++||||||||||||||||||||||||||||++|||||||+|||||++|++||++||+||
T Consensus 1 Y~~rFl~lY~kI~dp~nGYFS~~GiPYHsvETlivEAPDyGHeTTSEA~SY~~WLeAmyg~itgd~s~~~~AW~~mE~y~ 80 (620
)
T AAA91086.1|GH4 1 YKQRFLELYNKIHDPANGYFSPEGIPYHSVETLIVEAPDYGHETTSEAYSYYVWLEAMYGKITGDWSGFNKAWDTMEKYI 80 (620
)
Confidence 78999999999999999999999999999999999999999999999999999999999999999999999999999999

Q tr|G8M3C3|G8M3 111 IPSESIQKGMNRYNPSSPAGYADEFPLPDDYPAQIQSNVTVGQDPIHQELVSAYNTYAMYGMHWLVDVDNWYGYGT---- 186 (728

)
Q Consensus 111 ipsesiqkgmnrynpsspagyadefplpddypaqiqsnvtvgqdpihqelvsayntyamygmhwlvdvdnwygygt---- 186 (728
)
||++++||+|+.|||++|||||||+++|++||++|+++++||+|||++||+++||+++||+||||||||||||||+
T Consensus 81 IP~~~~Qp~~~~Ynp~~pAtya~E~~~P~~YPs~l~~~~~vG~DPi~~eL~saYgt~~iY~MHWLlDVDN~YGfG~~g~~ 160 (620
)
T AAA91086.1|GH4 81 IPSHQDQPTMSSYNPSSPATYAPEYDTPSQYPSQLDFNVPVGQDPIANELKSAYGTDDIYGMHWLLDVDNWYGFGNLGDG 160 (620
)
Confidence 9999999999999999999999999999999999999999999999999999999999999999999999999999

Q tr|G8M3C3|G8M3 187 GTNCTFINTYQRGEQESVFETVPHPSIEEFKYGGRQGFSDLFTAG-ETQPKWAFTIASDADGRLIQVQYWANKWAKEQGQ 265 (728

)
Q Consensus 187 gtnctfintyqrgeqesvfetvphpsieefkyggrqgfsdlftag-etqpkwaftiasdadgrliqvqywankwakeqgq 265 (728
)
+++|+||||||||+||||||||||||||+|||||+||||+||++| ++++|||||||||||||||||+|||++||+|||+
T Consensus 161 ~~~psyINTfQRG~qESvWeTvp~P~~d~fk~Gg~nGfldlFt~d~~ya~QwkYTnApDADARavQa~YwA~~Wa~e~G~ 240 (620
)
T AAA91086.1|GH4 161 TSGPSYINTFQRGEQESVWETVPHPSCEEFKYGGPNGFLDLFTKDSSYAKQWRYTNAPDADARAVQAAYWANQWAKEQGK 240 (620
)
Confidence 899999999999999999999999999999999999999999999 9999999999999999999999999999999999

Q tr|G8M3C3|G8M3 266 --NLSTLNAKAAKLGDYLRYSMFDKYFMKIG--AQGKTPASGYDSCHYLLAWYYAWGGAIAG-DWSWKIGCSHVHWGYQA 340 (728

)
Q Consensus 266 --nlstlnakaaklgdylrysmfdkyfmkig--aqgktpasgydschyllawyyawggaiag-dwswkigcshvhwgyqa 340 (728
)
+|+++++||+||||||||+|||||||||| +.+|++|+||||||||||||++|||++++ +|+|||||||+||||||
T Consensus 241 ~~~is~~~~KAaKmGDyLRY~mfDKYfkkiG~~~~s~~ag~GkdSaHYLlsWY~aWGG~~~~~~WaWrIG~Sh~H~GYQN 320 (620
)
T AAA91086.1|GH4 241 ESEISSTVAKAAKMGDYLRYAMFDKYFKKIGVGPSSCPAGTGKDSAHYLLSWYYAWGGALDGSGWAWRIGSSHAHFGYQN 320 (620
)
Confidence 99999999999999999999999999999 89999999999999999999999999999 99999999999999999

Q tr|G8M3C3|G8M3 341 PLAAYALANDPDLKPKSANGAKDWNSSFKRQVELYAWLQSAEGAIAGGVTNSVGGQYKSY-NGASTFYDMAYTYAPVYAD 419 (728

)
Q Consensus 341 plaayalandpdlkpksangakdwnssfkrqvelyawlqsaegaiaggvtnsvggqyksy-ngastfydmaytyapvyad 419 (728
)
||||||||++++|||||+|+++||++||+||||||+||||+||+|||||||||+|+|++| +|++|||||+|+++|||||
T Consensus 321 P~AAyaLs~~~~lkPks~ta~~DW~~SL~RQlEfy~wLQS~eG~iAGGaTNSW~G~Y~~~Psg~~TFygM~Yd~~PVY~D 400 (620
)
T AAA91086.1|GH4 321 PLAAYALSNDSDLKPKSPTAASDWAKSLDRQLEFYQWLQSAEGAIAGGATNSWNGRYETYPSGTSTFYGMAYDEHPVYHD 400 (620
)
Confidence 999999999999999999999999999999999999999999999999999999999999 9999999999999999999

Q tr|G8M3C3|G8M3 420 PPSNNWFGMQAWSMQRMCEVYYETGDSLAKEICDKWVAWAESVCEADIEAGTWKIPATLEWSGQPDTWRGTKPSNNNLHC 499 (728

)
Q Consensus 420 ppsnnwfgmqawsmqrmcevyyetgdslakeicdkwvawaesvceadieagtwkipatlewsgqpdtwrgtkpsnnnlhc 499 (728
)
||||+|||||+|+|||||||||+|||++||+||||||+|++++|+|+ ++|+|+||++|+|+|||||||+++++|+||||
T Consensus 401 PpSN~WfG~Q~Wsm~RvAeyYY~tGD~~ak~ildKWv~W~~~~~~~~-~dg~~~iPs~L~WsGqPDtW~gs~~~N~~lhv 479 (620
)
T AAA91086.1|GH4 401 PPSNRWFGMQAWSMQRVAEYYYVTGDARAKAILDKWVAWVKSNTTVN-SDGTFQIPSTLEWSGQPDTWNGSYTGNPNLHV 479 (620
)
Confidence 99999999999999999999999999999999999999999999999 88999999999999999999999999999999

Q tr|G8M3C3|G8M3 500 KVVNYGNDIGITGSLANAFLFYDQATQRWNGNTTLGKKAADKALAMLQVVWDTCRDQYGVGVKETNESLNRIFTQEVFIP 579 (728

)
Q Consensus 500 kvvnygndigitgslanaflfydqatqrwngnttlgkkaadkalamlqvvwdtcrdqygvgvketneslnriftqevfip 579 (728
)
+|+++|+|||||+||||||+||||++|+++ | ++||++||+|||+||++|||++||+++|+|+||+||++++||||
T Consensus 480 ~V~~yg~dvGva~s~A~tL~yYAa~sg~~~-d----~~ak~~Ak~LLD~~w~~~~d~~Gvs~~E~r~dy~Rf~d~~VYiP 554 (620
)
T AAA91086.1|GH4 480 TVTDYGQDVGVAASLAKTLMYYAAASGKYG-D----TAAKNLAKQLLDAMWKNYRDDKGVSTPETRGDYKRFFDQEVYIP 554 (620
)
Confidence 999999999999999999999999999888 7 88999999999999999999999999999999999999999999

Q tr|G8M3C3|G8M3 580 AGWTGKMPNGDVIQQGVKFIDIRSKYKDDPWYEGLKKQAEQGIPFEYTLHRFWHQVDYAVALGIA 644 (728)

Q Consensus 580 agwtgkmpngdviqqgvkfidirskykddpwyeglkkqaeqgipfeytlhrfwhqvdyavalgia 644 (728)
+||+|+|||||+|++|+|||||||+||+||+|++||++|++|++|+|+|||||+|+|||||+|+.
T Consensus 555 ~gwtG~mPnGD~I~~g~tFl~IRs~Yk~Dp~w~kvq~~l~gG~~p~f~YHRFWaQ~diA~A~g~y 619 (620)
T AAA91086.1|GH4 555 SGWTGTMPNGDVIKSGATFLDIRSKYKQDPDWPKVEAYLNGGAAPEFTYHRFWAQADIAMANGTY 619 (620)
Confidence 99999999999999999999999999999999999999999999999999999999999999863

No 2
>lcl|consensus
Probab=91.79 E-value=0.00051 Score=37.45 Aligned_cols=20 Identities=55% Similarity=0.811 Sum_probs=11.9 T
emplate_Neff=4.300

Q tr|G8M3C3|G8M3 668 DINFDGDINSIDYALLKAHL 687 (728)

Q Consensus 668 dinfdgdinsidyallkahl 687 (728)
|+|-||.+|++|++++|.++
T Consensus 1 DvN~DG~Vna~D~~~l~~~l 20 (21)
T lcl|consensus_ 1 DVNGDGKVNALDLALLKKYL 20 (21)
Confidence 45566666666666665554

No 3
>ABN51673.1|GH124|2-334|2.6e-219
Probab=52.47 E-value=0.096 Score=40.07 Aligned_cols=66 Identities=35% Similarity=0.533 Sum_probs=48.5 Tem
plate_Neff=1.400
Q tr|G8M3C3|G8M3 663 DIKLGDINFDGDINSIDYALLKAHLLGINKLSGDAL-KAADVDQNGDVNSIDYAKMKSYLLGISKDF 728 (728)
Q Consensus 663 diklgdinfdgdinsidyallkahllginklsgdal-kaadvdqngdvnsidyakmksyllgiskdf 728 (728)
.+..||.|-||-+|--||.|+|..|.-|.+...+.- -..+++....++.+|-.-+|.|||.+-++|
T Consensus 19 kav~GD~n~dgvv~isd~vl~k~~l~~~a~~~a~~d~w~g~vN~dd~I~D~d~~~~kryll~mir~~ 85 (318)
T ABN51673.1|GH1 19 KAVIGDVNADGVVNISDYVLMKRILRIIADFPADDDMWVGDVNGDDVINDIDCNYLKRYLLHMIREF 85 (318)
Confidence 567899999999999999999997766666543321 123444445577888888999999876553

No 4
>CAR68154.1|GH88|62-388|4.9e-137
Probab=10.51 E-value=2 Score=30.74 Aligned_cols=43 Identities=19% Similarity=0.234 Sum_probs=34.3 Templat
e_Neff=5.400

Q tr|G8M3C3|G8M3 421 PSNNWFGMQAWSMQRMCEVYYETGDSLAKEICDKWVAWAESVC 463 (728)

Q Consensus 421 psnnwfgmqawsmqrmcevyyetgdslakeicdkwvawaesvc 463 (728)
.+..|=-=|+|.|==.|..|..|||++--++-.+=+.+++++.
T Consensus 181 d~S~WsRGQAWaiYG~a~~yr~t~d~~yL~~A~~~a~yfl~~l 223 (329)
T CAR68154.1|GH8 181 DDSAWARGQAWAIYGFALAYRYTKDPEYLDTAKKVADYFLNRL 223 (329)
Confidence 3678999999999999999999999995555555555555555

No 5
>ACY49347.1|GH105|46-385|1.1e-131
Probab=6.37 E-value=4 Score=28.22 Aligned_cols=60 Identities=25% Similarity=0.330 Sum_probs=50.1 Template
_Neff=6.200

Q tr|G8M3C3|G8M3 324 DWSWKIGCSHVHWGYQAPLAAYALANDPDLKPKSANGAKDWNSSFKRQVELYAWLQSAEG 383 (728)

Q Consensus 324 dwswkigcshvhwgyqaplaayalandpdlkpksangakdwnssfkrqvelyawlqsaeg 383 (728)
.|+=.-|.|..+.|==|=-.+.||...-++-|+.........+.|++|++=..=+|+.+|
T Consensus 169 ~wa~~t~~s~~fW~RgnGW~~~aL~~~L~~lP~~~p~r~~l~~~~~~~~~al~~~Qd~~G 228 (329)
T ACY49347.1|GH1 169 NWADPTGGSPAFWGRGNGWVAMALVDVLELLPEDHPDRRFLIDILKEQAAALAKYQDESG 228 (329)
Confidence 444445667777777788889999999999998888889999999999998888999776

No 6
>QGI59602.1|GH16_22|78-291
Probab=5.38 E-value=4.9 Score=27.58 Aligned_cols=10 Identities=30% Similarity=0.245 Sum_probs=6.0 Templat
e_Neff=3.000

Q tr|G8M3C3|G8M3 391 NSVGGQYKSY 400 (728)

Q Consensus 391 nsvggqyksy 400 (728)
||-+..|-..
T Consensus 33 NS~nNvyie~ 42 (224)
T QGI59602.1|GH1 33 NSPNNVYIEK 42 (224)
Confidence 6666666555

No 7
>QGI59602.1|GH16_22|78-291
Probab=5.33 E-value=5 Score=27.55 Aligned_cols=18 Identities=28% Similarity=0.730 Sum_probs=9.8 Template_
Neff=3.000

Q tr|G8M3C3|G8M3 581 GWTGKMPNGDVIQQGVKF 598 (728)

Q Consensus 581 gwtgkmpngdviqqgvkf 598 (728)
.|+|.|.-|+...-++..
T Consensus 204 ~WsGnM~vg~sa~lqIqW 221 (224)
T QGI59602.1|GH1 204 SWSGNMSVGDSAYLQIQW 221 (224)
Confidence 366666666654444333

No 8
>AQA16748.1|GH5_51.hmm|7.4e-189|58-409
Probab=4.89 E-value=5.5 Score=28.57 Aligned_cols=37 Identities=32% Similarity=0.524 Sum_probs=28.0 Templa
te_Neff=2.200

Q tr|G8M3C3|G8M3 644 AEIFGYKPPK--GGSGGGETGDIKLGDINFDGDINSIDY 680 (728)

Q Consensus 644 aeifgykppk--ggsgggetgdiklgdinfdgdinsidy 680 (728)
|..+||.-|+ |.+|-|||.|.+..|+.-..-.+.++-
T Consensus 253 aHfYgYTGP~htGatg~get~dpRY~Dl~~~~l~~~l~~ 291 (351)
T AQA16748.1|GH5 253 AHFYGYTGPNHTGATGIGETHDPRYRDLSPAELAAVLDD 291 (351)
Confidence 5678998775 677789999999999877655555443

No 9
>CCF60459.1|GH5_12.hmm|1.2e-238|14-567
Probab=3.29 E-value=9.1 Score=28.28 Aligned_cols=27 Identities=26% Similarity=0.540 Sum_probs=17.1 Templa
te_Neff=4.100

Q tr|G8M3C3|G8M3 357 SANGAKDWNSSFKRQVELYAWLQSAEG 383 (728)

Q Consensus 357 sangakdwnssfkrqvelyawlqsaeg 383 (728)
.|.+++-|.+.-+|+=.-|-|-.+++-
T Consensus 298 np~G~saWl~~~~~~d~~ygw~r~~~w 324 (541)
T CCF60459.1|GH5 298 NPKGVSAWLSGEERDDKKYGWKRDPEW 324 (541)
Confidence 345667777777777666777655443

No 10
>ACI55886.1|GH25|58-236|2.7e-60
Probab=3.03 E-value=10 Score=22.20 Aligned_cols=41 Identities=20% Similarity=0.114 Sum_probs=30.1 Templat
e_Neff=7.700

Q tr|G8M3C3|G8M3 594 QGVKFIDIRSKY---KDDPWYEGLKKQAEQGIPFEYTLHRFWHQ 634 (728)

Q Consensus 594 qgvkfidirsky---kddpwyeglkkqaeqgipfeytlhrfwhq 634 (728)
+|..|.-||.-+ -.||.|..=-+....-..|.=.||-+.+.
T Consensus 18 ~gi~Fv~ikateG~~~~D~~f~~n~~~a~~aGl~~G~Yhf~~~~ 61 (174)
T ACI55886.1|GH2 18 SGVDFVIIKATEGTSYVDPYFASNWAGARAAGLPVGAYHFARPC 61 (174)
Confidence 389999999765 36888876555555556788889988854

- 12:48:16.066 INFO: Premerge done

- 12:48:16.066 INFO: Realigning 10 HMM-HMM alignments using Maximum Accuracy algorithm

- 12:48:16.115 INFO: 4 sequences belonging to 4 database HMMs found with an E-value < 0.001

- 12:48:16.115 INFO: Number of effective sequences of resulting query HMM: Neff = 2.41642

We can see that the exact protein was found in dbCAN in hit 1, but also some highly related proteins were found in hits
1-5. This query.a3m MSA can then be useful if we want to search a larger database like UniProt or Uniclust because it
includes this more diverse selection of related protein sequences.

Other hh-suite functions

hhsuite contains other functions which may be useful if you are working with MSA or HMMs. For more detailed
information, see the documentation at https://github.com/soedinglab/hh-suite/wiki

hhmake: Build an HMM from an input MSA

hhfilter: Filter an MSA by max sequence identity, coverage, and other criteria

hhalign: Calculate pairwise alignments etc. for two HMMs/MSAs

hhconsensus: Calculate the consensus sequence for an A3M/FASTA input file

reformat.pl: Reformat one or many MSAs

addss.pl: Add PSIPRED predicted secondary structure to an MSA or HHM file

hhmakemodel.pl: Generate MSAs or coarse 3D models from HHsearch or HHblits results

hhmakemodel.py: Generates coarse 3D models from HHsearch or HHblits results and modifies cif files such that they
are compatible with MODELLER

hhsuitedb.py: Build HHsuite database with prefiltering, packed MSA/HMM, and index files

splitfasta.pl: Split a multiple-sequence FASTA file into multiple single-sequence files

renumberpdb.pl: Generate PDB file with indices renumbered to match input sequence indices

HHPaths.pm: Configuration file with paths to the PDB, BLAST, PSIPRED etc. mergeali.pl: Merge MSAs in A3M format
according to an MSA of their seed sequences

pdb2fasta.pl: Generate FASTA sequence file from SEQRES records of globbed pdb files

cif2fasta.py: Generate a FASTA sequence from the pdbx_seq_one_letter_code entry of the entity_poly of globbed cif files

pdbfilter.pl: Generate representative set of PDB/SCOP sequences from pdb2fasta.pl output

pdbfilter.py: Generate representative set of PDB/SCOP sequences from cif2fasta.py output

References:

[1] Steinegger M, Meier M, Mirdita M, Vöhringer H, Haunsberger S J, and Söding J (2019) HH-suite3 for fast remote
homology detection and deep protein annotation, BMC Bioinformatics, 473. doi: 10.1186/s12859-019-3019-7

[2] Kunzmann, P., Mayer, B.E. & Hamacher, K. Substitution matrix based color schemes for sequence alignment
visualization. BMC Bioinformatics 21, 209 (2020). https://doi.org/10.1186/s12859-020-3526-6
[3]Identifying DNA and protein patterns with statistically significant alignments of multiple sequences.
https://www.researchgate.net/publication/12812078_

[4]https://github.com/soedinglab/hh-suite/wiki#what-are-hmm-hmm-comparisons-and-why-are-they-so-powerful

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ScanPy
ScanPy is a scalable toolkit for analyzing single-cell gene expression data. It includes methods for preprocessing,
visualization, clustering, pseudotime and trajectory inference, differential expression testing, and simulation of gene
regulatory networks. There are many advantage of using a Python-based platform to process scRNA-seq data including
increased processing efficiency and running speed as well as seamless integration with machine learning frameworks.

ANNDATA was presented alongside ScanPy as a generic class for handling annotated data matrices that can deal with
the sparsity inherent in gene expression data.

This tutorial is largely adapted from the original tutorials which can be found in Scanpy's read the docs and from this
notebook.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

Make sure you've installed Scanpy:

%conda install -c conda-forge scanpy python-igraph leidenalg

Collecting package metadata (current_repodata.json): done

Solving environment: done

# All requested packages already installed.

Note: you may need to restart the kernel to use updated packages.

# import necessary packages

import numpy as np
import pandas as pd
import scanpy as sc

sc.settings.verbosity = 3 # verbosity: errors (0), warnings (1), info (2), hints (3)

# see what package versions you have installed

sc.logging.print_versions()
# customize resolution and color of your figures
sc.settings.set_figure_params(dpi=80, facecolor='white')

# download the test data for this tutorial

!mkdir data
!wget http://cf.10xgenomics.com/samples/cell-exp/1.1.0/pbmc3k/pbmc3k_filtered_gene_bc_matrices.tar.gz -O data/pbmc3k_
!cd data; tar -xzf pbmc3k_filtered_gene_bc_matrices.tar.gz
!mkdir write

results_file = 'write/pbmc3k.h5ad' # the file that will store the analysis results

adata = sc.read_10x_mtx(
'data/filtered_gene_bc_matrices/hg19/', # the directory with the `.mtx` file
var_names='gene_symbols', # use gene symbols for the variable names (variables-axis index)
cache=True) # write a cache file for faster subsequent reading

... reading from cache file cache/data-filtered_gene_bc_matrices-hg19-matrix.h5ad

See [anndata-tutorials/getting-started] for a more comprehensive introduction to AnnData.

adata.var_names_make_unique() # this is unnecessary if using `var_names='gene_ids'` in `sc.read_10x_mtx`

# look at what the AnnData object contains

adata

AnnData object with n_obs × n_vars = 2700 × 32738

var: 'gene_ids'

Pre-processing
Check for highly expressed genes
Show genes that yield the highest fraction of counts in each single cell, across all cells. The
sc.pl.highest_expr_genes command normalizes counts per cell, and plots the genes that are most abundant in each
cell.

sc.pl.highest_expr_genes(adata, n_top=20, )

normalizing counts per cell

finished (0:00:00)

Note that MALAT1, a non-coding RNA that is known to be extremely abundant in many cells, ranks at the top.

Basic filtering: remove cells and genes with low expression or missing
values.
sc.pp.filter_cells(adata, min_genes=200)
sc.pp.filter_genes(adata, min_cells=3)

filtered out 19024 genes that are detected in less than 3 cells

Check mitochondrial genes for Quality Control

Let’s assemble some information about mitochondrial genes, which are important for quality control.

Citing from “Simple Single Cell” workflows (Lun, McCarthy & Marioni, 2017):

High proportions are indicative of poor-quality cells (Islam et al. 2014; Ilicic et al. 2016), possibly because of loss of
cytoplasmic RNA from perforated cells. The reasoning is that mitochondria are larger than individual transcript
molecules and less likely to escape through tears in the cell membrane.

With pp.calculate_qc_metrics , we can compute many metrics very efficiently.

adata.var['mt'] = adata.var_names.str.startswith('MT-') # annotate the group of mitochondrial genes as 'mt'

sc.pp.calculate_qc_metrics(adata, qc_vars=['mt'], percent_top=None, log1p=False, inplace=True)

A violin plot of some of the computed quality measures:

the number of genes expressed in the count matrix

the total counts per cell
the percentage of counts in mitochondrial genes

sc.pl.violin(adata, ['n_genes_by_counts', 'total_counts', 'pct_counts_mt'],

jitter=0.4, multi_panel=True)
Remove cells that have too many mitochondrial genes expressed or too many total counts. High proportions of
mitochondrial genes indicate poor-quality cells, potentially because of loss of cytoplasmic RNA from perforated cells.

sc.pl.scatter(adata, x='total_counts', y='pct_counts_mt')

sc.pl.scatter(adata, x='total_counts', y='n_genes_by_counts')

Filter data based on QC

Check current datset and filter it by slicing the AnnData object.

print(adata)

AnnData object with n_obs × n_vars = 2700 × 13714

obs: 'n_genes', 'n_genes_by_counts', 'total_counts', 'total_counts_mt', 'pct_counts_mt'
var: 'gene_ids', 'n_cells', 'mt', 'n_cells_by_counts', 'mean_counts', 'pct_dropout_by_counts', 'total_counts
'

# slice the adata object so you only keep genes and cells that pass the QC
adata = adata[adata.obs.n_genes_by_counts < 2500, :]
adata = adata[adata.obs.pct_counts_mt < 5, :]
print(adata)

View of AnnData object with n_obs × n_vars = 2638 × 13714

obs: 'n_genes', 'n_genes_by_counts', 'total_counts', 'total_counts_mt', 'pct_counts_mt'
var: 'gene_ids', 'n_cells', 'mt', 'n_cells_by_counts', 'mean_counts', 'pct_dropout_by_counts', 'total_counts
'
Data normalization
To correct differences in library sizes across cells, normalize the total read count of the data matrix to 10,000 reads per
cell so that counts become comparable among cells.

sc.pp.normalize_total(adata, target_sum=1e4)

normalizing counts per cell

finished (0:00:00)
/Users/paulinampaiz/opt/anaconda3/envs/deepchem/lib/python3.10/site-packages/scanpy/preprocessing/_normalization
.py:170: UserWarning: Received a view of an AnnData. Making a copy.
view_to_actual(adata)

Log transform the data for later use in differential gene expression as well as in visualizations. The natural logarithm is
used, and log1p means that an extra read is added to cells of the count matrix as a pseudo-read. See here for more
information on why log scale makes more sense for genomic data.

sc.pp.log1p(adata)

Identify highly-variable genes.

The function sc.pp.highly_variable_genes can detect marker genes that can help us identify cells based on a few
manually set parameters, including mininum mean expression, maximum mean expression, and minimum dispersion.
We will focus our analysis on such genes.

sc.pp.highly_variable_genes(adata, min_mean=0.0125, max_mean=3, min_disp=0.5)

extracting highly variable genes

finished (0:00:00)
--> added
'highly_variable', boolean vector (adata.var)
'means', float vector (adata.var)
'dispersions', float vector (adata.var)
'dispersions_norm', float vector (adata.var)

# visualize the highly variable genes with a plot

sc.pl.highly_variable_genes(adata)

Set the .raw attribute of the AnnData object to the normalized and logarithmized raw gene expression for later use in
differential testing and visualizations of gene expression. This simply freezes the state of the AnnData object.

adata.raw = adata

Filter the adata object so that only genes that are highly variable are kept.

adata = adata[:, adata.var.highly_variable]

Correct for the effects of counts per cell and mitochondrial gene
expression
Regress out effects of total counts per cell and the percentage of mitochondrial genes expressed. This can consume
some memory and take some time because the input data is sparse.

sc.pp.regress_out(adata, ['n_genes_by_counts', 'pct_counts_mt'])

regressing out ['n_genes_by_counts', 'pct_counts_mt']
sparse input is densified and may lead to high memory use
finished (0:00:11)

Center the data to zero and scale to unit variance

Use sc.pp.scale to center the average expression per gene to zero. Here we are also clipping scaled values that
exceed standard deviation of 10.

sc.pp.scale(adata, max_value=10)

Dimension reduction with PCA

We first use principal component analysis (PCA), a linear dimention-reduction technique, to reveal the main axes of
variation and denoise the data.

sc.tl.pca(adata, svd_solver='arpack')

computing PCA
on highly variable genes
with n_comps=50
finished (0:00:00)

We can make a scatter plot in the PCA coordinates, but we will not use that later on.

sc.pl.pca(adata, color="CST3")

The variance ratio plot lists contributions of individual principal components (PC) to the total variance in the data. This
piece of information helps us to choose an appropriate number of PCs in order to compute the neighborhood
relationships between the cells, for instance, using the clustering method Louvain sc.tl.louvain() or the embedding
method tSNE sc.tl.tsne() for dimension-reduction.

According to the authors of Scanpy, a rough estimate of the number of PCs does fine.

sc.pl.pca_variance_ratio(adata, log=True)

Save the result up to PCA analysis.

! mkdir -p write
adata.write(results_file)
Note that our adata object has following elements: observations annotation (obs), variables (var), unstructured
annotation (uns), multi-dimensional observations annotation (obsm), and multi-dimensional variables annotation (varm).
The meanings of these parameters are documented in the anndata package, available at anndata documentation.

adata

AnnData object with n_obs × n_vars = 2638 × 1838

obs: 'n_genes', 'n_genes_by_counts', 'total_counts', 'total_counts_mt', 'pct_counts_mt'
var: 'gene_ids', 'n_cells', 'mt', 'n_cells_by_counts', 'mean_counts', 'pct_dropout_by_counts', 'total_count
s', 'highly_variable', 'means', 'dispersions', 'dispersions_norm', 'mean', 'std'
uns: 'log1p', 'hvg', 'pca'
obsm: 'X_pca'
varm: 'PCs'

Computing and Embedding the neighborhood graph

Use the PCA representation of the data matrix to compute the neighborhood graph of cells.

sc.pp.neighbors(adata, n_neighbors=10, n_pcs=40)

The auhours of Scanpy suggest embedding the graph in two dimensions using UMAP (McInnes et al., 2018). UMAP is
potentially more faithful to the global connectivity of the manifold than tSNE, i.e., it better preserves trajectories.

sc.tl.umap(adata)

sc.pl.umap(adata, color=['CST3', 'NKG7', 'PPBP'])

As we set the .raw attribute of adata, the previous plots showed the “raw” (normalized, logarithmized, but
uncorrected) gene expression. You can also plot the scaled and corrected gene expression by explicitly stating that you
don’t want to use .raw .

sc.pl.umap(adata, color=['CST3', 'NKG7', 'PPBP'], use_raw=False)

In some ocassions, you might still observe disconnected clusters and similar connectivity violations. They can usually be
remedied by running:

tl.paga(adata)
pl.paga(adata, plot=False) # remove `plot=False` if you want to see the coarse-grained graph
tl.umap(adata, init_pos='paga')

Clustering the neighborhood graph

As with Seurat and many other frameworks, we recommend the Leiden graph-clustering method (community detection
based on optimizing modularity) by Traag et al. (2018). Note that Leiden clustering directly clusters the neighborhood
graph of cells, which we already computed in the previous section. Compared with the Louvain algorithm, the Leiden
algorithm yields communities that are guaranteed to be connected. When applied iteratively, the Leiden algorithm
converges to a partition in which all subsets of all communicities are locally optimally assigned. Last but not least, it
runs faster.

sc.tl.leiden(adata)

Plot the clusters using sc.pl.umap . Note that the color parameter accepts both individual genes and the clustering
method (leiden in this case).

sc.pl.umap(adata, color=['leiden', 'CST3', 'NKG7'])

We save the result again.

adata.write(results_file)

Identifying marker genes

Compute a ranking for the highly differential genes in each cluster. For this, by default, the .raw attribute of AnnData
is used in case it has been initialized before. The simplest and fastest method to do so is the t-test. Other methods
include Wilcoxon rank-sum (Mann-Whitney-U) test, MAST, limma, DESeq2, and diffxpy by the Theis lab. The authours of
Scanpy reccomend using the Wilcoxon rank-sum test in publications.
The Wilcoxon's test
For simplicity, we start with the Mann-Whitney-U test. The null hypothesis is that the rank of a gene in a cluster is the
same as its rank in all cells. The alternative hypothesis is that the rank of a gene in a cluster is much higher than its rank
in all cells (one-sided). The function sc.tl.rank_genes_groups performs the test, and sc.pl.rank_genes_groups
plots the top genes.

sc.tl.rank_genes_groups(adata, groupby='leiden', method='wilcoxon')

sc.pl.rank_genes_groups(adata, n_genes=15, sharey=False)

sc.settings.verbosity = 2 # reduce the verbosity

adata.write(results_file) # write the output to the results file

The Student's t-test

An alternative to the non-parametric Wilcoxon test is the t-test.

sc.tl.rank_genes_groups(adata, 'leiden', method='t-test')

sc.pl.rank_genes_groups(adata, n_genes=15, sharey=False)

As an alternative, let us rank genes using logistic regression. For instance, this has been suggested by Natranos et al.
(2018). The essential difference is that here, we use a multi-variate appraoch whereas conventional differential tests are
uni-variate. Clark et al. (2014) has more details.

sc.tl.rank_genes_groups(adata, 'leiden', method="logreg")

sc.pl.rank_genes_groups(adata, n_genes=15, sharey=False)

Let us also define a list of marker genes for later reference.

marker_genes = ['IL7R', 'CD79A', 'MS4A1', 'CD8A', 'CD8B', 'LYZ', 'CD14',

'LGALS3', 'S100A8', 'GNLY', 'NKG7', 'KLRB1',
'FCGR3A', 'MS4A7', 'FCER1A', 'CST3', 'PPBP']

Listing signatures using the results of the Wilcoxon's test

We use the results of the Wilcoxon's test for downstream analysis. Reload the object that has been save with the
Wilcoxon Rank-Sum test result.

adata = sc.read(results_file)

Show the 10 top ranked genes per cluster 0, 1, …, 7 in a dataframe.

pd.DataFrame(adata.uns['rank_genes_groups']['names']).head(5)

Get a table with the scores and groups.

result = adata.uns['rank_genes_groups']
groups = result['names'].dtype.names
pd.DataFrame(
{group + '_' + key[:1]: result[key][group]
for group in groups for key in ['names', 'pvals']}).head(5)

Compare to a single cluster:

sc.tl.rank_genes_groups(adata, 'leiden', groups=['0'], reference='1', method='wilcoxon')

sc.pl.rank_genes_groups(adata, groups=['0'], n_genes=20)

If we want a more detailed view for a certain group, use sc.pl.rank_genes_groups_violin .

sc.pl.rank_genes_groups_violin(adata, groups='0', n_genes=8)

If you want to compare a certain gene across groups, use the following.

sc.pl.violin(adata, ['CST3', 'NKG7', 'PPBP'], groupby='leiden')

Actually mark the cell types.

new_cluster_names = [
'CD4 T', 'CD14 Monocytes',
'B', 'CD8 T',
'NK', 'FCGR3A Monocytes',
'Dendritic', 'Megakaryocytes']
adata.rename_categories('leiden', new_cluster_names)

# plot the UMAP

sc.pl.umap(adata, color='leiden', legend_loc='on data', title='', frameon=False, save='.pdf')

Now that we annotated the cell types, let us visualize the marker genes.

sc.pl.dotplot(adata, marker_genes, groupby='leiden');

There is also a very compact violin plot.

sc.pl.stacked_violin(adata, marker_genes, groupby='leiden', rotation=90);

During the course of this analysis, the AnnData accumulated the following annotations.

adata

If you want to save your results:

adata.write(results_file, compression='gzip') # `compression='gzip'` saves disk space, but slows down writing and su

Get a rough overview of the file using h5ls, which has many options - for more details see here. The file format might
still be subject to further optimization in the future. All reading functions will remain backwards-compatible, though.

If you want to share this file with people who merely want to use it for visualization, a simple way to reduce the file size
is by removing the dense scaled and corrected data matrix. The file still contains the raw data used in the visualizations
in adata.raw .

adata.raw.to_adata().write('./write/pbmc3k_withoutX.h5ad')

If you want to export to “csv”, you have the following options:

# Export single fields of the annotation of observations

# adata.obs[['n_counts', 'louvain_groups']].to_csv(
# './write/pbmc3k_corrected_louvain_groups.csv')

# Export single columns of the multidimensional annotation

# adata.obsm.to_df()[['X_pca1', 'X_pca2']].to_csv(
# './write/pbmc3k_corrected_X_pca.csv')

# Or export everything except the data using `.write_csvs`.

# Set `skip_data=False` if you also want to export the data.
# adata.write_csvs(results_file[:-5], )
Deep Probabilistic Analysis of Single-Cell Omics Data
Recordings at single-cell resolution can give us a better understanding of the biological differences in our sample. As
sequencing technologies and instruments have become better and cheaper, generating single-cell data is becoming
more popular. In order to derive meaningful biological insights, it is important to select reliable analysis tools such as
the one we will cover in this tutorial.

scvi-tools (single-cell variational inference tools) is a package for probabilistic modeling and analysis of single-cell omics
data, built on top of PyTorch and AnnData that aims to address some of the limitations that arise when developing and
implementing probabilistic models. scvi-tools is used in tandem with Scanpy for which Deepchem also offers a tutorial.
In the broader analysis pipeline, scVI sits downstream of initial quality control (QC)-driven preprocessing and generates
outputs that may be further interpreted via general single-cell analysis tools.

In this introductory tutorial, we go through the different steps of an scvi-tools workflow. While we focus on scVI in this
tutorial, the API is consistent across all models. Please note that this tutorial was largely adapted from the one provided
by scvi-tools and you can head to their page to find more information.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

# install necessary packages

!pip install --quiet scvi-colab
from scvi_colab import install
install()

import scvi
import scanpy as sc
import matplotlib.pyplot as plt

# set preferences for figures and plots

sc.set_figure_params(figsize=(4, 4))

# for white background of figures (only for docs rendering)

%config InlineBackend.print_figure_kwargs={'facecolor' : "w"}
%config InlineBackend.figure_format='retina'

Global seed set to 0

Loading and preparing data

Let us first load a subsampled version of the heart cell atlas dataset described in Litviňuková et al. (2020). scvi-tools has
many "built-in" datasets as well as support for loading arbitrary .csv , .loom , and .h5ad (AnnData) files. Please see
our tutorial on data loading for more examples.

Litviňuková, M., Talavera-López, C., Maatz, H., Reichart, D., Worth, C. L., Lindberg, E. L., ... & Teichmann, S. A.
(2020). Cells of the adult human heart. Nature, 588(7838), 466-472.

Important
All scvi-tools models require AnnData objects as input.

adata = scvi.data.heart_cell_atlas_subsampled()

INFO File data/hca_subsampled_20k.h5ad already downloaded

Now we preprocess the data to remove, for example, genes that are very lowly expressed and other outliers. For these
tasks we prefer the Scanpy preprocessing module.

sc.pp.filter_genes(adata, min_counts=3)

In scRNA-seq analysis, it's popular to normalize the data. These values are not used by scvi-tools, but given their
popularity in other tasks as well as for visualization, we store them in the anndata object separately (via the .raw
attribute).
Important

Unless otherwise specified, scvi-tools models require the raw counts (not log library size normalized).

adata.layers["counts"] = adata.X.copy() # preserve counts

sc.pp.normalize_total(adata, target_sum=1e4)
sc.pp.log1p(adata)
adata.raw = adata # freeze the state in `.raw`

Finally, we perform feature selection, to reduce the number of features (genes in this case) used as input to the scvi-
tools model. For best practices of how/when to perform feature selection, please refer to the model-specific tutorial. For
scVI, we recommend anywhere from 1,000 to 10,000 HVGs, but it will be context-dependent.

sc.pp.highly_variable_genes(
adata,
n_top_genes=1200,
subset=True,
layer="counts",
flavor="seurat_v3",
batch_key="cell_source"
)

Now it's time to run setup_anndata() , which alerts scvi-tools to the locations of various matrices inside the anndata.
It's important to run this function with the correct arguments so scvi-tools is notified that your dataset has batches,
annotations, etc. For example, if batches are registered with scvi-tools, the subsequent model will correct for batch
effects. See the full documentation for details.

In this dataset, there is a "cell_source" categorical covariate, and within each "cell_source", multiple "donors", "gender"
and "age_group". There are also two continuous covariates we'd like to correct for: "percent_mito" and "percent_ribo".
These covariates can be registered using the categorical_covariate_keys argument. If you only have one
categorical covariate, you can also use the batch_key argument instead.

scvi.model.SCVI.setup_anndata(
adata,
layer="counts",
categorical_covariate_keys=["cell_source", "donor"],
continuous_covariate_keys=["percent_mito", "percent_ribo"]
)

Warning

If the adata is modified after running setup_anndata , please run setup_anndata again, before creating an
instance of a model.

Creating and training a model

While we highlight the scVI model here, the API is consistent across all scvi-tools models and is inspired by that of scikit-
learn. For a full list of options, see the scvi documentation.

model = scvi.model.SCVI(adata)

We can see an overview of the model by printing it.

model

SCVI Model with the following params:

n_hidden: 128, n_latent: 10, n_layers: 1, dropout_rate: 0.1, dispersion: gene,
gene_likelihood: zinb, latent_distribution: normal
Training status: Not Trained

Important
All scvi-tools models run faster when using a GPU. By default, scvi-tools will use a GPU if one is found to be available.
Please see the installation page for more information about installing scvi-tools when a GPU is available.

model.train()
GPU available: True, used: True
TPU available: False, using: 0 TPU cores
IPU available: False, using: 0 IPUs
LOCAL_RANK: 0 - CUDA_VISIBLE_DEVICES: [0]
Epoch 400/400: 100%|██████████| 400/400 [05:43<00:00, 1.16it/s, loss=284, v_num=1]

Saving and loading

Saving consists of saving the model neural network weights, as well as parameters used to initialize the model.

# model.save("my_model/")

# model = scvi.model.SCVI.load("my_model/", adata=adata, use_gpu=True)

Obtaining model outputs

latent = model.get_latent_representation()

It's often useful to store the outputs of scvi-tools back into the original anndata, as it permits interoperability with
Scanpy.

adata.obsm["X_scVI"] = latent

The model.get...() functions default to using the anndata that was used to initialize the model. It's possible to also
query a subset of the anndata, or even use a completely independent anndata object as long as the anndata is
organized in an equivalent fashion.

adata_subset = adata[adata.obs.cell_type == "Fibroblast"]

latent_subset = model.get_latent_representation(adata_subset)

INFO Received view of anndata, making copy.

INFO:scvi.model.base._base_model:Received view of anndata, making copy.
INFO Input AnnData not setup with scvi-tools. attempting to transfer AnnData setup
INFO:scvi.model.base._base_model:Input AnnData not setup with scvi-tools. attempting to transfer AnnData setup

denoised = model.get_normalized_expression(adata_subset, library_size=1e4)

denoised.iloc[:5, :5]

INFO Received view of anndata, making copy.

GTCAAGTCATGCCACG-1-HCAHeart7702879 0.343808 0.118372 1.945633 0.062702 4.456603

GAGTCATTCTCCGTGT-1-HCAHeart8287128 1.552080 0.275485 1.457585 0.013442 14.617260

CCTCTGATCGTGACAT-1-HCAHeart7702881 5.157080 0.295140 1.195748 0.143792 2.908867

CGCCATTCATCATCTT-1-H0035_apex 0.352172 0.019281 0.570386 0.105633 6.325405

TCGTAGAGTAGGACTG-1-H0015_septum 0.290155 0.040910 0.400771 0.723409 8.142258

Let's store the normalized values back in the anndata.

adata.layers["scvi_normalized"] = model.get_normalized_expression(
library_size=10e4
)

Interoperability with Scanpy

Scanpy is a powerful python library for visualization and downstream analysis of scRNA-seq data. We show here how to
feed the objects produced by scvi-tools into a scanpy workflow.

Visualization without batch correction

Warning

We use UMAP to qualitatively assess our low-dimension embeddings of cells. We do not advise using UMAP or any
similar approach quantitatively. We do recommend using the embeddings produced by scVI as a plug-in replacement
of what you would get from PCA, as we show below.
First, we demonstrate the presence of nuisance variation with respect to nuclei/whole cell, age group, and donor by
plotting the UMAP results of the top 30 PCA components for the raw count data.

# run PCA then generate UMAP plots

sc.tl.pca(adata)
sc.pp.neighbors(adata, n_pcs=30, n_neighbors=20)
sc.tl.umap(adata, min_dist=0.3)

sc.pl.umap(
adata,
color=["cell_type"],
frameon=False,
)
sc.pl.umap(
adata,
color=["donor", "cell_source"],
ncols=2,
frameon=False,
)

We see that while the cell types are generally well separated, nuisance variation plays a large part in the variation of
the data.

Visualization with batch correction (scVI)

Now, let us try using the scVI latent space to generate the same UMAP plots to see if scVI successfully accounts for
batch effects in the data.

# use scVI latent space for UMAP generation

sc.pp.neighbors(adata, use_rep="X_scVI")
sc.tl.umap(adata, min_dist=0.3)

sc.pl.umap(
adata,
color=["cell_type"],
frameon=False,
)
sc.pl.umap(
adata,
color=["donor", "cell_source"],
ncols=2,
frameon=False,
)
We can see that scVI was able to correct for nuisance variation due to nuclei/whole cell, age group, and donor, while
maintaining separation of cell types.

Clustering on the scVI latent space

The user will note that we imported curated labels from the original publication. Our interface with scanpy makes it easy
to cluster the data with scanpy from scVI's latent space and then reinject them into scVI (e.g., for differential
expression).

# neighbors were already computed using scVI

sc.tl.leiden(adata, key_added="leiden_scVI", resolution=0.5)

sc.pl.umap(
adata,
color=["leiden_scVI"],
frameon=False,
)

Differential expression
We can also use many scvi-tools models for differential expression. For further details on the methods underlying these
functions as well as additional options, please see the API docs.

adata.obs.cell_type.head()
AACTCCCCACGAGAGT-1-HCAHeart7844001 Myeloid
ATAACGCAGAGCTGGT-1-HCAHeart7829979 Ventricular_Cardiomyocyte
GTCAAGTCATGCCACG-1-HCAHeart7702879 Fibroblast
GGTGATTCAAATGAGT-1-HCAHeart8102858 Endothelial
AGAGAATTCTTAGCAG-1-HCAHeart8102863 Endothelial
Name: cell_type, dtype: category
Categories (11, object): ['Adipocytes', 'Atrial_Cardiomyocyte', 'Endothelial', 'Fibroblast', ..., 'Neuronal', '
Pericytes', 'Smooth_muscle_cells', 'Ventricular_Cardiomyocyte']

For example, a 1-vs-1 DE test is as simple as:

de_df = model.differential_expression(
groupby="cell_type",
group1="Endothelial",
group2="Fibroblast"
)
de_df.head()

DE...: 100%|██████████| 1/1 [00:00<00:00, 3.07it/s]

proba_de proba_not_de bayes_factor scale1 scale2 pseudocounts delta lfc_mean lfc_median lfc_

SOX17 0.9998 0.0002 8.516943 0.001615 0.000029 0.0 0.25 6.222365 6.216846 1.9675

SLC9A3R2 0.9996 0.0004 7.823621 0.010660 0.000171 0.0 0.25 5.977907 6.049340 1.6721

ABCA10 0.9990 0.0010 6.906745 0.000081 0.006355 0.0 0.25 -8.468659 -9.058912 2.9593

EGFL7 0.9986 0.0014 6.569875 0.008471 0.000392 0.0 0.25 4.751251 4.730982 1.5463

VWF 0.9984 0.0016 6.436144 0.014278 0.000553 0.0 0.25 5.013347 5.029471 1.7587

5 rows × 22 columns

We can also do a 1-vs-all DE test, which compares each cell type with the rest of the dataset:

de_df = model.differential_expression(
groupby="cell_type",
)
de_df.head()

DE...: 100%|██████████| 11/11 [00:03<00:00, 3.08it/s]

proba_de proba_not_de bayes_factor scale1 scale2 pseudocounts delta lfc_mean lfc_median lfc_std

CIDEC 0.9988 0.0012 6.724225 0.002336 0.000031 0.0 0.25 7.082959 7.075700 2.681833

ADIPOQ 0.9988 0.0012 6.724225 0.003627 0.000052 0.0 0.25 7.722131 7.461277 3.332577

GPAM 0.9986 0.0014 6.569875 0.025417 0.000202 0.0 0.25 7.365266 7.381156 2.562121

PLIN1 0.9984 0.0016 6.436144 0.004482 0.000048 0.0 0.25 7.818194 7.579515 2.977385

GPD1 0.9974 0.0026 5.949637 0.002172 0.000044 0.0 0.25 6.543847 6.023436 2.865962

5 rows × 22 columns

We now extract top markers for each cluster using the DE results.

markers = {}
cats = adata.obs.cell_type.cat.categories
for i, c in enumerate(cats):
cid = "{} vs Rest".format(c)
cell_type_df = de_df.loc[de_df.comparison == cid]

cell_type_df = cell_type_df[cell_type_df.lfc_mean > 0]

cell_type_df = cell_type_df[cell_type_df["bayes_factor"] > 3]

cell_type_df = cell_type_df[cell_type_df["non_zeros_proportion1"] > 0.1]

markers[c] = cell_type_df.index.tolist()[:3]
sc.tl.dendrogram(adata, groupby="cell_type", use_rep="X_scVI")

sc.pl.dotplot(
adata,
markers,
groupby='cell_type',
dendrogram=True,
color_map="Blues",
swap_axes=True,
use_raw=True,
standard_scale="var",
)

We can also visualize the scVI normalized gene expression values with the layer option.

sc.pl.heatmap(
adata,
markers,
groupby='cell_type',
layer="scvi_normalized",
standard_scale="var",
dendrogram=True,
figsize=(8, 12)
)

Logging information
Verbosity varies in the following way:

logger.setLevel(logging.WARNING) will show a progress bar.

logger.setLevel(logging.INFO) will show global logs including the number of jobs done.
logger.setLevel(logging.DEBUG) will show detailed logs for each training (e.g the parameters tested).

This function's behaviour can be customized, please refer to its documentation for information about the different
parameters available.

In general, you can use scvi.settings.verbosity to set the verbosity of the scvi package. Note that verbosity
corresponds to the logging levels of the standard python logging module. By default, that verbosity level is set to
INFO (=20). As a reminder the logging levels are:

Level Numeric value

CRITICAL 50

ERROR 40

WARNING 30

INFO 20

DEBUG 10

NOTSET 0

Reference
If you use scvi-tools in your research, please consider citing

@article{Gayoso2022,
author={Gayoso, Adam and Lopez, Romain and Xing, Galen and Boyeau, Pierre and Valiollah Pour Amiri, Valeh
title={A Python library for probabilistic analysis of single-cell omics data},
journal={Nature Biotechnology},
year={2022},
month={Feb},
day={07},
issn={1546-1696},
doi={10.1038/s41587-021-01206-w},
url={https://doi.org/10.1038/s41587-021-01206-w}
}

along with the publicaton describing the model used.

This tutorial was contributed to Deepchem by:

@manual{Bioinformatics,
title={Deep Probabilistic Analysis of Single-Cell Omics Data},
organization={DeepChem},
author={Paiz, Paulina},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Deep_probabilistic_analysis
year={2022},
}
Cell Counting
Cell counting is a fundamental task found in many biological research and medical diagnostic processes. It underlies
decisions in cell culture, drug development, and disease analysis. However, traditional manual cell counting methods
are often time-consuming and prone to human error. This variability can hinder research progress and lead to
inconsistencies across studies.

Although cell counting machines exist, they are expensive and may not be readily available to all researchers.
Automating cell counting using machine learning offers a powerful solution to this problem. ML-powered cell counters
can quickly and accurately analyze large volumes of cell samples, freeing up researchers' time and minimizing
inconsistencies.

Ready to build your own cell counter and revolutionize your research efficiency? This tutorial equips you with the
knowledge and skills to create a customized tool that streamlines your cell counting needs.

Colab
This tutorial and the rest in this sequence can be done in Google colab. If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem as dc
dc.__version__

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eepchem) (2.8.2)
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2023.4)
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n->deepchem) (3.3.0)
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.3.0)
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>pandas->deepchem) (1.16.0)
'2.7.2.dev'

Now we will import all the necessary packages and functions

import numpy as np
import matplotlib.pyplot as plt

from deepchem.data import NumpyDataset

from deepchem.models.torch_models import CNN

BBBC Datasets
We used the image set BBBC002v1 [Carpenter et al., Genome Biology, 2006] from the Broad Bioimage Benchmark
Collection [Ljosa et al., Nature Methods, 2012] for this tutorial.

The Broad Bioimage Benchmark Collection Dataset 002 (BBBC002) contains images of Drosophila Kc167 cells. The
ground truth labels consist of cell counts. Full details about this dataset are present at
https://bbbc.broadinstitute.org/BBBC002.

For counting cells, our dataset needs to have images as inputs and the corresponding cell counts as the ground truth
labels. We have several BBBC datasets that can be loaded using the deepchem package. These datasets are an
extension to MoleculeNet and can be accessed through dc.molnet .

The BBBC002 dataset consists of 60 images, each 512x512 pixels in size, which are split into train, validation and test
sets in a 80/10/10 split by default.
We also use splitter='random' in order to ensure that these images are randomly split into the train, validation and
test sets in the above mention ratios.

bbbc2_dataset = dc.molnet.load_bbbc002(splitter='random')
tasks, dataset, transforms = bbbc2_dataset
train, val, test = dataset

train_x, train_y, train_w, train_ids = train.X, train.y, train.w, train.ids

val_x, val_y, val_w, val_ids = val.X, val.y, val.w, val.ids
test_x, test_y, test_w, test_ids = test.X, test.y, test.w, test.ids

Now that we've loaded the dataset and randomly split it, let's take a look at the data.

print(f"Shape of train data: {train_x.shape}")

print(f"Shape of train labels: {train_y.shape}")

Shape of train data: (40, 512, 512)

Shape of train labels: (40,)

We can confirm that a sample from our dataset is in the form of a 512x512 image. Let's visualize this sample:

i = 2

plt.figure(figsize=(5, 5))
plt.imshow(train_x[i])
plt.title(f"Cell Count: {train_y[i]}")
plt.show()

Now let's prepare the data for the model.

PyTorch based CNN Models require that images be in the shape of (C, H, W), wherein 'C' is the number of input
channels, 'H' is the height of the image and 'W' is the width of the image. So we will reshape the data.

train_x = np.array(train_x.reshape(-1, 512, 512, 1), dtype=np.float32)

train_y = np.array(train_y.reshape(-1), dtype=np.float32)

val_x = np.array(val_x.reshape(-1, 512, 512, 1), dtype=np.float32)

val_y = np.array(val_y.reshape(-1), dtype=np.float32)

test_x = np.array(test_x.reshape(-1, 512, 512, 1), dtype=np.float32)

test_y = np.array(test_y.reshape(-1), dtype=np.float32)

train_data = NumpyDataset(train_x, train_y)

val_data = NumpyDataset(val_x, val_y)
test_data = NumpyDataset(test_x, test_y)

Creating and training our model

We will use the rms_score metric for our Validation Callback in order to monitor the performance of the model during
training.

For more information on how to use callbacks, refer to this tutorial on Advanced Model Training

We will use the CNN model from the deepchem package. Since cell counting is a relational problem, we will use the
regression mode.

We will use a 2D CNN model, with 6 hidden layers of the following sizes [32, 64, 128, 128, 64, 32] and a kernel size of 3
across all the filters, you can modify both the kernel size and the number of filters per layer. We have also used average
pooling made residual connections and added dropout layers between subsequent layers in order to improve
performance. Feel free to experiment with various models.

regression_metric = dc.metrics.Metric(dc.metrics.rms_score)

model = CNN(n_tasks=1, n_features=1, dims=2, layer_filters = [32, 64, 128, 128, 64, 32], kernel_size=3, learning_rate
mode='regression', padding='same', batch_size=4, residual=True, dropouts=0.1, pool_type='average')

callback = dc.models.ValidationCallback(val_data, 10, [regression_metric])

avg_loss = model.fit(train_data, nb_epoch=20, callbacks=callback)

/usr/local/lib/python3.10/dist-packages/torch/nn/modules/lazy.py:180: UserWarning: Lazy modules are a new featur

e under heavy development so changes to the API or functionality can happen at any moment.
warnings.warn('Lazy modules are a new feature under heavy development '
Step 10 validation: rms_score=43.5554
Step 20 validation: rms_score=61.2546
Step 30 validation: rms_score=39.8772
Step 40 validation: rms_score=52.2475
Step 50 validation: rms_score=42.5802
Step 60 validation: rms_score=38.1957
Step 70 validation: rms_score=72.0341
Step 80 validation: rms_score=35.5798
Step 90 validation: rms_score=46.5774
Step 100 validation: rms_score=31.5153
Step 110 validation: rms_score=38.8215
Step 120 validation: rms_score=35.6907
Step 130 validation: rms_score=29.9797
Step 140 validation: rms_score=28.0428
Step 150 validation: rms_score=44.3926
Step 160 validation: rms_score=37.7657
Step 170 validation: rms_score=34.5076
Step 180 validation: rms_score=26.8319
Step 190 validation: rms_score=26.6618
Step 200 validation: rms_score=26.4627

Evaluating the performance of our model

Now let's use mean_absolute_error as our test metric and print out the results of our model. We have also created a
graph of True vs Predicted values in order to visualize our model's performance

We can see that the model performs fairly well with a test loss of about 14.6. This means that on average, the predicted
number of cells for a sample image is off by 14.6 cells when compared to the ground truth. Although this seems like a
very high value for test loss, we will see that a difference of about 15 cells is actually not bad for this particular task.

test_metric = dc.metrics.Metric(dc.metrics.mean_absolute_error)

preds = np.array(model.predict(train_data), dtype=np.uint32)

print("Train loss: ", test_metric.compute_metric(train_y, preds))

preds = np.array(model.predict(val_data), dtype=np.uint32)

print("Val Loss: ", test_metric.compute_metric(val_y, preds))

preds = np.array(model.predict(test_data), dtype=np.uint32)

print("Test Loss: ", test_metric.compute_metric(test_y, preds))

plt.figure(figsize=(4, 4))
plt.title("True vs. Predicted")
plt.plot(test_y, color='red', label='true')
plt.plot(preds, color='blue', label='preds')
plt.legend()
plt.show()
Train loss: 19.05
Val Loss: 22.2
Test Loss: 14.6

Let us print out the mean cell count of our predictions and compare them with the ground truth. We will also print out
the maximum difference between the ground truth and the prediction from the test set.

print(f"Mean of True Values: {np.mean(test_y):.2f}")

print(f"Mean of Predictions: {np.mean(preds):.2f}")

diff = []
for i in range(len(test_y)):
diff.append(abs(test_y[i] - preds[i]))

print(f"Max of Difference: {np.max(diff)}")

Mean of True Values: 87.60

Mean of Predictions: 87.80
Max of Difference: 31.0

We can observe that the averages of our predictions and the ground truth are very close with a difference of just 0.20.
Although we see a maximum difference of 31 cells between the prediction and true value, when we take into account
the Test Loss , the close proximity of the means of predictions and the true labels, and the small size of our test set,
we can say that our model performs fairly well.

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sciences. Join the conversation!

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Bioinformatics,
title={Cell Counting Tutorial},
organization={DeepChem},
author={Menezes, Aaron},
howpublished = {\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Cell_Counting_Tutorial.ipyn
year={2024},
}
Introduction To Material Science
Table of Contents:
Introduction
Setup
Featurizers
Crystal Featurizers
Compound Featurizers
Datasets
Predicting structural properties of a crystal
Further Reading

Introduction
One of the most exciting applications of machine learning in the recent time is it's application to material science
domain. DeepChem helps in development and application of machine learning to solid-state systems. As a starting point
of applying machine learning to material science domain, DeepChem provides material science datasets as part of the
MoleculeNet suite of datasets, data featurizers and implementation of popular machine learning algorithms specific to
material science domain. This tutorial serves as an introduction of using DeepChem for machine learning related tasks
in material science domain.

Traditionally, experimental research were used to find and characterize new materials. But traditional methods have
high limitations by constraints of required resources and equipments. Material science is one of the booming areas
where machine learning is making new in-roads. The discovery of new material properties holds key to lot of problems
like climate change, development of new semi-conducting materials etc. DeepChem acts as a toolbox for using machine
learning in material science.

This tutorial can also be used in Google colab. If you'd like to open this notebook in colab, you can use the following link.
This notebook is made to run without any GPU support.

Open in Colab

!pip install --pre deepchem

DeepChem for material science will also require the additiona libraries pymatgen and matminer . These two libraries
assist machine learning in material science. For graph neural network models which we will be used in the backend,
DeepChem requires dgl library. All these can be installed using pip . Note when using locally, install a higher version
of the jupyter notebook (>6.5.5, here on colab).

!pip install -q pymatgen==2023.12.18

!pip install -q matminer==0.9.0
!pip install -q dgl
!pip install -q tqdm

import deepchem as dc
dc.__version__

from tqdm import tqdm

import matplotlib.pyplot as plt

import pymatgen as mg
from pymatgen import core as core

import os
os.environ['DEEPCHEM_DATA_DIR'] = os.getcwd()

Featurizers
Material Structure Featurizers
Crystal are geometric structures which has to be featurized for using in machine learning algorithms. The following
featurizers provided by DeepChem helps in featurizing crystals:

The SineCoulombMatrix featurizer a crystal by calculating sine coulomb matrix for the crystals. It can be called using
dc.featurizers.SineCoulombMatrix function. [1]
The CGCNNFeaturizer calculates structure graph features of crystals. It can be called using
dc.featurizers.CGCNNFeaturizer function. [2]
The LCNNFeaturizer calculates the 2-D Surface graph features in 6 different permutations. It can be used using the
utility dc.feat.LCNNFeaturizer . [3]

[1] Faber et al. “Crystal Structure Representations for Machine Learning Models of Formation Energies”, Inter. J.
Quantum Chem. 115, 16, 2015. https://arxiv.org/abs/1503.07406

[2] T. Xie and J. C. Grossman, “Crystal graph convolutional neural networks for an accurate and interpretable prediction
of material properties”, Phys. Rev. Lett. 120, 2018, https://arxiv.org/abs/1710.10324

[3] Jonathan Lym, Geun Ho Gu, Yousung Jung, and Dionisios G. Vlachos, Lattice Convolutional Neural Network Modeling
of Adsorbate Coverage Effects, J. Phys. Chem. C 2019 https://pubs.acs.org/doi/10.1021/acs.jpcc.9b03370

Example: Featurizing a crystal

In this part, we will be using pymatgen for representing the crystal structure of Caesium Chloride and calculate
structure graph features using CGCNNFeaturizer .

The CsCl crystal is a cubic lattice with the chloride atoms lying upon the lattice points at the edges of the cube, while
the caesium atoms lie in the holes in the center of the cubes. The green colored atoms are the caesium atoms in this
crystal structure and chloride atoms are the grey ones.

Source: Wikipedia

# the lattice paramter of a cubic cell

a = 4.2
lattice = core.Lattice.cubic(a)

# Atoms in a crystal
atomic_species = ["Cs", "Cl"]
# Coordinates of atoms in a crystal
cs_coords = [0, 0, 0]
cl_coords = [0.5, 0.5, 0.5]
structure = mg.core.Structure(lattice, atomic_species, [cs_coords, cl_coords])
structure

Structure Summary
Lattice
abc : 4.2 4.2 4.2
angles : 90.0 90.0 90.0
volume : 74.08800000000001
A : 4.2 0.0 0.0
B : 0.0 4.2 0.0
C : 0.0 0.0 4.2
pbc : True True True
PeriodicSite: Cs (0.0, 0.0, 0.0) [0.0, 0.0, 0.0]
PeriodicSite: Cl (2.1, 2.1, 2.1) [0.5, 0.5, 0.5]

In above code sample, we first defined a cubic lattice using the cubic lattice parameter a . Then, we created a structure
with atoms in the crystal and their coordinates as features. A nice introduction to crystallographic coordinates can be
found here. Once a structure is defined, it can be featurized using CGCNN Featurizer. Featurization of a crystal using
CGCNNFeaturizer returns a DeepChem GraphData object which can be used for machine learning tasks.

featurizer = dc.feat.CGCNNFeaturizer()
features = featurizer.featurize([structure])
features[0]

GraphData(node_features=[2, 92], edge_index=[2, 24], edge_features=[24, 41])

Material Composition Featurizers

The above part discussed about using DeepChem for featurizing crystal structures. Here, we will be seeing about
featurizing material compositions. DeepChem supports the following material composition featurizers:

The ElementPropertyFingerprint can be used to find fingerprint of elements based on elemental stoichiometry. It can
be used using a call to dc.featurizers.ElementPropertyFingerprint . [4]
The ElemNetFeaturizer returns a vector containing fractional compositions of each element in the compound. It can
be used using a call to dc.feat.ElemNetFeaturizer . [5]

[4] Ward, L., Agrawal, A., Choudhary, A. et al. A general-purpose machine learning framework for predicting properties
of inorganic materials. npj Comput Mater 2, 16028 (2016). https://doi.org/10.1038/npjcompumats.2016.28

[5] Jha, D., Ward, L., Paul, A. et al. "ElemNet: Deep Learning the Chemistry of Materials From Only Elemental
Composition", Sci Rep 8, 17593 (2018). https://doi.org/10.1038/s41598-018-35934-y

Example: Featurizing a compund

In the below example, we featurize Ferric Oxide (Fe2O3) using ElementPropertyFingerprint featurizer . The
featurizer returns the compounds elemental stoichoimetry properties as features.

comp = core.Composition("Fe2O3")
featurizer = dc.feat.ElementPropertyFingerprint()
features = featurizer.featurize([comp])
features[0]

/usr/local/lib/python3.10/dist-packages/pymatgen/core/periodic_table.py:186: UserWarning: No data available for

electrical_resistivity for O
warnings.warn(f"No data available for {item} for {self.symbol}")
/usr/local/lib/python3.10/dist-packages/pymatgen/core/periodic_table.py:186: UserWarning: No data available for
bulk_modulus for O
warnings.warn(f"No data available for {item} for {self.symbol}")
/usr/local/lib/python3.10/dist-packages/pymatgen/core/periodic_table.py:186: UserWarning: No data available for
coefficient_of_linear_thermal_expansion for O
warnings.warn(f"No data available for {item} for {self.symbol}")
array([1.83000000e+00, 3.44000000e+00, 1.61000000e+00, 2.79600000e+00,
1.13844192e+00, 2.00000000e+00, 4.00000000e+00, 2.00000000e+00,
2.80000000e+00, 1.41421356e+00, 8.00000000e+00, 1.60000000e+01,
8.00000000e+00, 1.28000000e+01, 5.65685425e+00, 2.00000000e+00,
3.00000000e+00, 1.00000000e+00, 2.40000000e+00, 7.07106781e-01,
1.59994000e+01, 5.58450000e+01, 3.98456000e+01, 3.19376400e+01,
2.81750940e+01, 6.00000000e-01, 1.40000000e+00, 8.00000000e-01,
9.20000000e-01, 5.65685425e-01, 6.10000000e+01, 1.01000000e+02,
4.00000000e+01, 8.50000000e+01, 2.82842712e+01, 0.00000000e+00,
0.00000000e+00, 0.00000000e+00, 0.00000000e+00, 0.00000000e+00,
3.17500000e+02, 4.91000000e+03, 4.59250000e+03, 2.15450000e+03,
3.24738789e+03, 2.65800000e-02, 8.00000000e+01, 7.99734200e+01,
3.20159480e+01, 5.65497476e+01, 5.48000000e+01, 1.81100000e+03,
1.75620000e+03, 7.57280000e+02, 1.24182093e+03, 0.00000000e+00,
0.00000000e+00, 0.00000000e+00, 0.00000000e+00, 0.00000000e+00,
0.00000000e+00, 0.00000000e+00, 0.00000000e+00, 0.00000000e+00,
0.00000000e+00])

Datasets
DeepChem has the following material properties dataset as part of MoleculeNet suite of datasets. These datasets can be
used for a variety of tasks in material science like predicting structure formation energy, metallicity of a compound etc.

The Band Gap dataset contains 4604 experimentally measured band gaps for inorganic crystal structure
compositions. The dataset can be loaded using dc.molnet.load_bandgap utility.
The Perovskite dataset contains 18928 perovskite structures and their formation energies. It can be loaded using a
call to dc.molnet.load_perovskite .
The Formation Energy dataset contains 132752 calculated formation energies and inorganic crystal structures from
the Materials Project database. It can be loaded using a call to dc.molnet.load_mp_formation_energy .
The Metallicity dataset contains 106113 inorganic crystal structures from the Materials Project database labeled as
metals or nonmetals. It can be loaded using dc.molnet.load_mp_metallicity utility.

In the below example, we will demonstrate loading perovskite dataset and use it to predict formation energy of new
crystals. Perovskite structures are structures adopted by many oxides. Ideally it is a cubic structure but non-cubic
variants also exists. Each datapoint in the perovskite dataset contains the lattice structure as a
pymatgen.core.Structure object and the formation energy of the corresponding structure. It can be used by calling
for machine learning tasks by calling dc.molnet.load_perovskite utility. The utility takes care of loading, featurizing
and splitting the dataset for machine learning tasks.

dataset_config = {"reload": True, "featurizer": dc.feat.CGCNNFeaturizer(), "transformers": []}

tasks, datasets, transformers = dc.molnet.load_perovskite(**dataset_config)
train_dataset, valid_dataset, test_dataset = datasets

train_dataset.get_data_shape

deepchem.data.datasets.DiskDataset.get_data_shape
def get_data_shape() -> Shape

Gets array shape of datapoints in this dataset.

Predicting Formation Energy

Along with the dataset and featurizers, DeepChem also provide implementation of various machine learning algorithms
which can be used on the fly for material science applications. For predicting formation energy, we use CGCNNModel as
described in the paper [1].

model = dc.models.CGCNNModel(mode='regression', batch_size=256, learning_rate=0.0008)

losses = []

for _ in tqdm(range(10), desc="Training"):

loss = model.fit(train_dataset, nb_epoch=1)
losses.append(loss)

plt.plot(losses)

Training: 100%|██████████| 10/10 [11:26<00:00, 68.65s/it]

[<matplotlib.lines.Line2D at 0x7967a9a126e0>]

Once fitting the model, we evaluate the performance of the model using mean squared error metric since it is a
regression task. For selection a metric, dc.metrics.mean_squared_error function can be used and we evaluate the
model by calling dc.model.evaluate .`

metric = dc.metrics.Metric(dc.metrics.mean_absolute_error)
print("Training set score:", model.evaluate(train_dataset, [metric], transformers))
print("Test set score:", model.evaluate(test_dataset, [metric], transformers))

Training set score: {'mean_absolute_error': 0.1310973839991837}

Test set score: {'mean_absolute_error': 0.13470105945654667}
The original paper achieved a MAE of 0.130 eV/atom on the same dataset (with a 60:20:20 split, instead of the 80:10:10
being used in this tutorial).

Further Reading
For further reading on getting started on using machine learning for material science, here are two great resources:

Getting Started in Material Informatics

A Collection of Open Source Material Informatics Resources

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Using Reinforcement Learning to Play Pong
This tutorial demonstrates using reinforcement learning to train an agent to play Pong. This task isn't directly related to
chemistry, but video games make an excellent demonstration of reinforcement learning techniques.

Colab
This tutorial and the rest in this sequence can be done in Google Colab (although the visualization at the end doesn't
work correctly on Colab, so you might prefer to run this tutorial locally). If you'd like to open this notebook in colab, you
can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

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Instructions for updating:
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!pip install "gym[atari,accept-rom-license]"

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Reinforcement Learning
Reinforcement learning involves an agent that interacts with an environment. In this case, the environment is the video
game and the agent is the player. By trial and error, the agent learns a policy that it follows to perform some task
(winning the game). As it plays, it receives rewards that give it feedback on how well it is doing. In this case, it receives
a positive reward every time it scores a point and a negative reward every time the other player scores a point.

The first step is to create an Environment that implements this task. Fortunately, OpenAI Gym already provides an
implementation of Pong (and many other tasks appropriate for reinforcement learning). DeepChem's GymEnvironment
class provides an easy way to use environments from OpenAI Gym. We could just use it directly, but in this case we
subclass it and preprocess the screen image a little bit to make learning easier.

import deepchem as dc
import numpy as np

class PongEnv(dc.rl.GymEnvironment):
def __init__(self):
super(PongEnv, self).__init__('Pong-v4')
self._state_shape = (80, 80)

@property
def state(self):
# Crop everything outside the play area, reduce the image size,
# and convert it to black and white.
state_array = self._state
cropped = state_array[34:194, :, :]
reduced = cropped[0:-1:2, 0:-1:2]
grayscale = np.sum(reduced, axis=2)
bw = np.zeros(grayscale.shape, dtype=np.float32)
bw[grayscale != 233] = 1
return bw

def deepcopy(self, memo):

return PongEnv()

env = PongEnv()

Next we create a model to implement our policy. This model receives the current state of the environment (the pixels
being displayed on the screen at this moment) as its input. Given that input, it decides what action to perform. In Pong
there are three possible actions at any moment: move the paddle up, move it down, or leave it where it is. The policy
model produces a probability distribution over these actions. It also produces a value output, which is interpreted as an
estimate of how good the current state is. This turns out to be important for efficient learning.

The model begins with two convolutional layers to process the image. That is followed by a dense (fully connected) layer
to provide plenty of capacity for game logic. We also add a small Gated Recurrent Unit (GRU). That gives the network a
little bit of memory, so it can keep track of which way the ball is moving. Just from the screen image, you cannot tell
whether the ball is moving to the left or to the right, so having memory is important.

We concatenate the dense and GRU outputs together, and use them as inputs to two final layers that serve as the
network's outputs. One computes the action probabilities, and the other computes an estimate of the state value
function.

We also provide an input for the initial state of the GRU, and return its final state at the end. This is required by the
learning algorithm.

import torch
import torch.nn as nn
import torch.nn.functional as F

class PongPolicy(dc.rl.Policy):
def __init__(self):
super(PongPolicy, self).__init__(['action_prob', 'value', 'rnn_state'], [np.zeros(16, dtype=np.float32)])

def create_model(self, **kwargs):

class TestModel(nn.Module):
def __init__(self):
super(TestModel, self).__init__()
# Convolutional layers
self.conv1 = nn.Conv2d(1, 16, kernel_size=8, stride=4)
self.conv2 = nn.Conv2d(16, 32, kernel_size=4, stride=2)
self.fc1 = nn.Linear(2048, 256)
self.gru = nn.GRU(256, 16, batch_first = True)
self.action_prob = nn.Linear(272, env.n_actions)
self.value = nn.Linear(272, 1)
def forward(self, inputs):
state = (torch.from_numpy((inputs[0])))
rnn_state = (torch.from_numpy(inputs[1]))
reshaped = state.view(-1, 1, 80, 80)
conv1 = F.relu(self.conv1(reshaped))
conv2 = F.relu(self.conv2(conv1))
conv2 = conv2.view(conv2.size(0), -1)
x = F.relu(self.fc1(conv2))
reshaped_x = x.view(1, -1, 256)
#x = torch.flatten(x, 1)
gru_out, rnn_final_state = self.gru(reshaped_x, rnn_state.unsqueeze(0))
rnn_final_state = rnn_final_state.view(-1,16)
gru_out = gru_out.view(-1, 16)
concat = torch.cat((x, gru_out), dim=1)
#concat = concat.view(-1, 272)
action_prob = F.softmax(self.action_prob(concat), dim=-1)
value = self.value(concat)
return action_prob, value, rnn_final_state
return TestModel()
policy = PongPolicy()

We will optimize the policy using the Advantage Actor Critic (A2C) algorithm. There are lots of hyperparameters we
could specify at this point, but the default values for most of them work well on this problem. The only one we need to
customize is the learning rate.

import torch.nn.functional as F
from deepchem.rl.torch_rl.torch_a2c import A2C

from deepchem.models.optimizers import Adam

a2c = A2C(env, policy, model_dir='model', optimizer=Adam(learning_rate=0.0002))

Optimize for as long as you have patience to. By 1 million steps you should see clear signs of learning. Around 3 million
steps it should start to occasionally beat the game's built in AI. By 7 million steps it should be winning almost every
time. Running on my laptop, training takes about 20 minutes for every million steps.

# Change this to train as many steps as you have patience for.

a2c.fit(1000)

c:\Users\HP\anaconda3\envs\deep\lib\site-packages\gym\utils\passive_env_checker.py:233: DeprecationWarning: `np.

bool8` is a deprecated alias for `np.bool_`. (Deprecated NumPy 1.24)
if not isinstance(terminated, (bool, np.bool8)):
Let's watch it play and see how it does!

# This code doesn't work well on Colab

env.reset()
while not env.terminated:
env.env.render()
env.step(a2c.select_action(env.state))

c:\Users\HP\anaconda3\envs\deep\lib\site-packages\gym\utils\passive_env_checker.py:289: UserWarning: WARN: No re

nder fps was declared in the environment (env.metadata['render_fps'] is None or not defined), rendering may occu
r at inconsistent fps.
logger.warn(

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Gitter

The DeepChem Gitter hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Uncertainty in Deep Learning
A common criticism of deep learning models is that they tend to act as black boxes. A model produces outputs, but
doesn't given enough context to interpret them properly. How reliable are the model's predictions? Are some predictions
more reliable than others? If a model predicts a value of 5.372 for some quantity, should you assume the true value is
between 5.371 and 5.373? Or that it's between 2 and 8? In some fields this situation might be good enough, but not in
science. For every value predicted by a model, we also want an estimate of the uncertainty in that value so we can
know what conclusions to draw based on it.

DeepChem makes it very easy to estimate the uncertainty of predicted outputs (at least for the models that support it—
not all of them do). Let's start by seeing an example of how to generate uncertainty estimates. We load a dataset,
create a model, train it on the training set, predict the output on the test set, and then derive some uncertainty
estimates.

Colab
This tutorial and the rest in this sequence are designed to be done in Google colab. If you'd like to open this notebook in
colab, you can use the following link.

Open in Colab

!pip install --pre deepchem

import deepchem
deepchem.__version__

We'll use the Delaney dataset from the MoleculeNet suite to run our experiments in this tutorial. Let's load up our
dataset for our experiments, and then make some uncertainty predictions.

import deepchem as dc
import numpy as np
import matplotlib.pyplot as plot

tasks, datasets, transformers = dc.molnet.load_delaney()

train_dataset, valid_dataset, test_dataset = datasets

model = dc.models.MultitaskRegressor(len(tasks), 1024, uncertainty=True)

model.fit(train_dataset, nb_epoch=20)
y_pred, y_std = model.predict_uncertainty(test_dataset)

All of this looks exactly like any other example, with just two differences. First, we add the option uncertainty=True
when creating the model. This instructs it to add features to the model that are needed for estimating uncertainty.
Second, we call predict_uncertainty() instead of predict() to produce the output. y_pred is the predicted
outputs. y_std is another array of the same shape, where each element is an estimate of the uncertainty (standard
deviation) of the corresponding element in y_pred . And that's all there is to it! Simple, right?

Of course, it isn't really that simple at all. DeepChem is doing a lot of work to come up with those uncertainties. So now
let's pull back the curtain and see what is really happening. (For the full mathematical details of calculating uncertainty,
see https://arxiv.org/abs/1703.04977)

To begin with, what does "uncertainty" mean? Intuitively, it is a measure of how much we can trust the predictions.
More formally, we expect that the true value of whatever we are trying to predict should usually be within a few
standard deviations of the predicted value. But uncertainty comes from many sources, ranging from noisy training data
to bad modelling choices, and different sources behave in different ways. It turns out there are two fundamental types
of uncertainty we need to take into account.

Aleatoric Uncertainty
Consider the following graph. It shows the best fit linear regression to a set of ten data points.

# Generate some fake data and plot a regression line.

x = np.linspace(0, 5, 10)
y = 0.15*x + np.random.random(10)
plot.scatter(x, y)
fit = np.polyfit(x, y, 1)
line_x = np.linspace(-1, 6, 2)
plot.plot(line_x, np.poly1d(fit)(line_x))
plot.show()
The line clearly does not do a great job of fitting the data. There are many possible reasons for this. Perhaps the
measuring device used to capture the data was not very accurate. Perhaps y depends on some other factor in addition
to x , and if we knew the value of that factor for each data point we could predict y more accurately. Maybe the
relationship between x and y simply isn't linear, and we need a more complicated model to capture it. Regardless of
the cause, the model clearly does a poor job of predicting the training data, and we need to keep that in mind. We
cannot expect it to be any more accurate on test data than on training data. This is known as aleatoric uncertainty.

How can we estimate the size of this uncertainty? By training a model to do it, of course! At the same time it is learning
to predict the outputs, it is also learning to predict how accurately each output matches the training data. For every
output of the model, we add a second output that produces the corresponding uncertainty. Then we modify the loss
function to make it learn both outputs at the same time.

Epistemic Uncertainty
Now consider these three curves. They are fit to the same data points as before, but this time we are using 10th degree
polynomials.

plot.figure(figsize=(12, 3))
line_x = np.linspace(0, 5, 50)
for i in range(3):
plot.subplot(1, 3, i+1)
plot.scatter(x, y)
fit = np.polyfit(np.concatenate([x, [3]]), np.concatenate([y, [i]]), 10)
plot.plot(line_x, np.poly1d(fit)(line_x))
plot.show()

Each of them perfectly interpolates the data points, yet they clearly are different models. (In fact, there are infinitely
many 10th degree polynomials that exactly interpolate any ten data points.) They make identical predictions for the
data we fit them to, but for any other value of x they produce different predictions. This is called epistemic uncertainty.
It means the data does not fully constrain the model. Given the training data, there are many different models we could
have found, and those models make different predictions.

The ideal way to measure epistemic uncertainty is to train many different models, each time using a different random
seed and possibly varying hyperparameters. Then use all of them for each input and see how much the predictions vary.
This is very expensive to do, since it involves repeating the whole training process many times. Fortunately, we can
approximate the same effect in a less expensive way: by using dropout.

Recall that when you train a model with dropout, you are effectively training a huge ensemble of different models all at
once. Each training sample is evaluated with a different dropout mask, corresponding to a different random subset of
the connections in the full model. Usually we only perform dropout during training and use a single averaged mask for
prediction. But instead, let's use dropout for prediction too. We can compute the output for lots of different dropout
masks, then see how much the predictions vary. This turns out to give a reasonable estimate of the epistemic
uncertainty in the outputs.

Uncertain Uncertainty?
Now we can combine the two types of uncertainty to compute an overall estimate of the error in each output:
This is the value DeepChem reports. But how much can you trust it? Remember how I started this tutorial: deep learning
models should not be used as black boxes. We want to know how reliable the outputs are. Adding uncertainty estimates
does not completely eliminate the problem; it just adds a layer of indirection. Now we have estimates of how reliable the
outputs are, but no guarantees that those estimates are themselves reliable.

Let's go back to the example we started with. We trained a model on the SAMPL training set, then generated predictions
and uncertainties for the test set. Since we know the correct outputs for all the test samples, we can evaluate how well
we did. Here is a plot of the absolute error in the predicted output versus the predicted uncertainty.

abs_error = np.abs(y_pred.flatten()-test_dataset.y.flatten())
plot.scatter(y_std.flatten(), abs_error)
plot.xlabel('Standard Deviation')
plot.ylabel('Absolute Error')
plot.show()

The first thing we notice is that the axes have similar ranges. The model clearly has learned the overall magnitude of
errors in the predictions. There also is clearly a correlation between the axes. Values with larger uncertainties tend on
average to have larger errors. (Strictly speaking, we expect the absolute error to be less than the predicted uncertainty.
Even a very uncertain number could still happen to be close to the correct value by chance. If the model is working well,
there should be more points below the diagonal than above it.)

Now let's see how well the values satisfy the expected distribution. If the standard deviations are correct, and if the
errors are normally distributed (which is certainly not guaranteed to be true!), we expect 95% of the values to be within
two standard deviations, and 99% to be within three standard deviations. Here is a histogram of errors as measured in
standard deviations.

plot.hist(abs_error/y_std.flatten(), 20)
plot.show()

All the values are in the expected range, and the distribution looks roughly Gaussian although not exactly. Perhaps this
indicates the errors are not normally distributed, but it may also reflect inaccuracies in the uncertainties. This is an
important reminder: the uncertainties are just estimates, not rigorous measurements. Most of them are pretty good, but
you should not put too much confidence in any single value.

Congratulations! Time to join the Community!

Congratulations on completing this tutorial notebook! If you enjoyed working through the tutorial, and want to continue
working with DeepChem, we encourage you to finish the rest of the tutorials in this series. You can also help the
DeepChem community in the following ways:
Star DeepChem on GitHub
Starring DeepChem on GitHub helps build awareness of the DeepChem project and the tools for open source drug
discovery that we're trying to build.

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sciences. Join the conversation!
Open in Colab

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import numpy as np
import functools
try:
import jax
import jax.numpy as jnp
import haiku as hk
import optax
from deepchem.models import PINNModel, JaxModel
from deepchem.data import NumpyDataset
from deepchem.models.optimizers import Adam
from jax import jacrev
has_haiku_and_optax = True
except:
has_haiku_and_optax = False

Given Physical Data

We have a 10 random points between

and its corresponding value f(x)

We know that data follows an underlying physical rule that

import matplotlib.pyplot as plt

give_size = 10
in_given = np.linspace(-2 * np.pi, 2 * np.pi, give_size)
out_given = np.cos(in_given) + 0.1*np.random.normal(loc=0.0, scale=1, size=give_size)

# red for numpy.sin()

plt.figure(figsize=(13, 7))

plt.scatter(in_given, out_given, color = 'green', marker = "o")

plt.xlabel("x --> ", fontsize=18)
plt.ylabel("f (x) -->", fontsize=18)
plt.legend(["Supervised Data"], prop={'size': 16}, loc ="lower right")

plt.title("Data of our physical system", fontsize=18)

Text(0.5, 1.0, 'Data of our physical system')

From simple integeration, we can easily solve the diffrential equation and the solution will be -

import matplotlib.pyplot as plt

test = np.expand_dims(np.linspace(-2.5 * np.pi, 2.5 * np.pi, 100), 1)

out_array = np.cos(test)

plt.figure(figsize=(13, 7))
plt.plot(test, out_array, color = 'blue', alpha = 0.5)
plt.scatter(in_given, out_given, color = 'green', marker = "o")
plt.xlabel("x --> ", fontsize=18)
plt.ylabel("f (x) -->", fontsize=18)
plt.legend(["Actual data" ,"Supervised Data"], prop={'size': 16}, loc ="lower right")

plt.title("Data of our physical system", fontsize=18)

Text(0.5, 1.0, 'Data of our physical system')

Building a Simple Neural Network Model -
We define a simple Feed-forward Neural Network with 2 hidden layers of size 256 & 128 neurons.

# defining the Haiku model

# A neural network is defined as a function of its weights & operations.

# NN(x) = F(x, W)

# forward function defines the F which describes the mathematical operations like Matrix & dot products, Signmoid fun
# W is the init_params

def f(x):
net = hk.nets.MLP(output_sizes=[256, 128, 1], activation=jax.nn.softplus)
val = net(x)
return val

init_params, forward_fn = hk.transform(f)

rng = jax.random.PRNGKey(500)
params = init_params(rng, np.random.rand(1000, 1))

/usr/local/lib/python3.7/dist-packages/jax/_src/numpy/lax_numpy.py:3634: UserWarning: Explicitly requested dtype

float64 requested in zeros is not available, and will be truncated to dtype float32. To enable more dtypes, set
the jax_enable_x64 configuration option or the JAX_ENABLE_X64 shell environment variable. See https://github.com
/google/jax#current-gotchas for more.
lax._check_user_dtype_supported(dtype, "zeros")

Fitting a simple Neural Network solution to the Physical

Data
train_dataset = NumpyDataset(np.expand_dims(in_given, axis=1), np.expand_dims(out_given, axis=1))
rms_loss = lambda pred, tar, w: jnp.mean(optax.l2_loss(pred, tar))
# JaxModel Working
nn_model = JaxModel(
forward_fn,
params,
rms_loss,
batch_size=100,
learning_rate=0.001,
log_frequency=2)
nn_model.fit(train_dataset, nb_epochs=10000, deterministic=True)

/usr/local/lib/python3.7/dist-packages/deepchem/models/jax_models/jax_model.py:160: UserWarning: JaxModel is sti

ll in active development and all features may not yet be implemented
'JaxModel is still in active development and all features may not yet be implemented'
2.1729056921826473e-11

dataset_test = NumpyDataset(test)
nn_output = nn_model.predict(dataset_test)

plt.figure(figsize=(13, 7))
plt.plot(test, out_array, color = 'blue', alpha = 0.5)
plt.scatter(in_given, out_given, color = 'green', marker = "o")
plt.plot(test, nn_output, color = 'red', marker = "o", alpha = 0.7)
plt.xlabel("x --> ", fontsize=18)
plt.ylabel("f (x) -->", fontsize=18)
plt.legend(["Actual data", "Vanilla NN", "Supervised Data"], prop={'size': 16}, loc ="lower right")

plt.title("Data of our physical system", fontsize=18)

Text(0.5, 1.0, 'Data of our physical system')

Learning to fit the Data using the underlying Diffrential
equation
Lets ensure that final output of the neural network satisfies the diffrential equation as a loss function-

def create_eval_fn(forward_fn, params):

"""
Calls the function to evaluate the model
"""

@jax.jit
def eval_model(x, rng=None):

bu = forward_fn(params, rng, x)
return jnp.squeeze(bu)

return eval_model

def gradient_fn(forward_fn, loss_outputs, initial_data):

"""
This function calls the gradient function, to implement the backpropagation
"""
boundary_data = initial_data['X0']
boundary_target = initial_data['u0']

@jax.jit
def model_loss(params, target, weights, rng, x_train):

@functools.partial(jax.vmap, in_axes=(None, 0))

def periodic_loss(params, x):
"""
diffrential equation => grad(f(x)) = - sin(x)
minimize f(x) := grad(f(x)) + sin(x)
"""
x = jnp.expand_dims(x, 0)
u_x = jacrev(forward_fn, argnums=(2))(params, rng, x)
return u_x + jnp.sin(x)

u_pred = forward_fn(params, rng, boundary_data)

loss_u = jnp.mean((u_pred - boundary_target)**2)

f_pred = periodic_loss(params, x_train)

loss_f = jnp.mean((f_pred**2))

return loss_u + loss_f

return model_loss

initial_data = {
'X0': jnp.expand_dims(in_given, 1),
'u0': jnp.expand_dims(out_given, 1)
}
opt = Adam(learning_rate=1e-3)
pinn_model= PINNModel(
forward_fn=forward_fn,
params=params,
initial_data=initial_data,
batch_size=1000,
optimizer=opt,
grad_fn=gradient_fn,
eval_fn=create_eval_fn,
deterministic=True,
log_frequency=1000)

# defining our training data. We feed 100 points between [-2.5pi, 2.5pi] without the labels,
# which will be used as the differential loss(regulariser)
X_f = np.expand_dims(np.linspace(-3 * np.pi, 3 * np.pi, 1000), 1)
dataset = NumpyDataset(X_f)
pinn_model.fit(dataset, nb_epochs=3000)

/usr/local/lib/python3.7/dist-packages/deepchem/models/jax_models/pinns_model.py:157: UserWarning: PinnModel is

still in active development and we could change the design of the API in the future.
'PinnModel is still in active development and we could change the design of the API in the future.'
/usr/local/lib/python3.7/dist-packages/deepchem/models/jax_models/jax_model.py:160: UserWarning: JaxModel is sti
ll in active development and all features may not yet be implemented
'JaxModel is still in active development and all features may not yet be implemented'
0.026332732232287527

import matplotlib.pyplot as plt

pinn_output = pinn_model.predict(dataset_test)

plt.figure(figsize=(13, 7))
plt.plot(test, out_array, color = 'blue', alpha = 0.5)
plt.scatter(in_given, out_given, color = 'green', marker = "o")
# plt.plot(test, nn_output, color = 'red', marker = "x", alpha = 0.3)
plt.scatter(test, pinn_output, color = 'red', marker = "o", alpha = 0.7)

plt.xlabel("x --> ", fontsize=18)

plt.ylabel("f (x) -->", fontsize=18)
plt.legend(["Actual data" ,"Supervised Data", "PINN"], prop={'size': 16}, loc ="lower right")

plt.title("Data of our physical system", fontsize=18)

Text(0.5, 1.0, 'Data of our physical system')

Comparing the results between PINN & Vanilla NN model
plt.figure(figsize=(13, 7))
# plt.plot(test, out_array, color = 'blue', alpha = 0.5)
# plt.scatter(in_given, out_given, color = 'green', marker = "o")
plt.scatter(test, nn_output, color = 'blue', marker = "x", alpha = 0.3)
plt.scatter(test, pinn_output, color = 'red', marker = "o", alpha = 0.7)

plt.xlabel("x --> ", fontsize=18)

plt.ylabel("f (x) -->", fontsize=18)
plt.legend(["Vanilla NN", "PINN"], prop={'size': 16}, loc ="lower right")

plt.title("Data of our physical system", fontsize=18)

Text(0.5, 1.0, 'Data of our physical system')

About Neural ODE : Using Torchdiffeq with Deepchem
Author : Anshuman Mishra : Linkedin

Open in Colab

Before getting our hands dirty with code , let us first understand little bit about what Neural ODEs are ?

NeuralODEs and torchdiffeq

NeuralODE stands for "Neural Ordinary Differential Equation. You heard right. Let me guess . Your first impression of the
word is : "Has it something to do with differential equations that we studied in the school ?"

Spot on ! Let's see the formal definition as stated by the original paper :

Neural ODEs are a new family of deep neural network models. Instead of specifying a discrete
sequence of
hidden layers, we parameterize the derivative of the hidden state using a neural network.

The output of the network is computed using a blackbox differential equation solver.These are
continuous-depth models that have constant memory
cost, adapt their evaluation strategy to each input, and can explicitly trade numerical
precision for speed.

In simple words perceive NeuralODEs as yet another type of layer like Linear, Conv2D, MHA...

In this tutorial we will be using torchdiffeq. This library provides ordinary differential equation (ODE) solvers
implemented in PyTorch framework. The library provides a clean API of ODE solvers for usage in deep learning
applications. As the solvers are implemented in PyTorch, algorithms in this repository are fully supported to run on the
GPU.

What will you learn after completing this tutorial ?

1. How to implement a Neural ODE in a Neural Network ?
2. Using torchdiffeq with deepchem.

Installing Libraries

!pip install torchdiffeq

!pip install --pre deepchem
Collecting torchdiffeq
Downloading torchdiffeq-0.2.2-py3-none-any.whl (31 kB)
Requirement already satisfied: torch>=1.3.0 in /usr/local/lib/python3.7/dist-packages (from torchdiffeq) (1.10.0
+cu111)
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diffeq) (1.21.5)
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orchdiffeq) (3.10.0.2)
Installing collected packages: torchdiffeq
Successfully installed torchdiffeq-0.2.2
Collecting deepchem
Downloading deepchem-2.6.1-py3-none-any.whl (608 kB)
|████████████████████████████████| 608 kB 8.9 MB/s
Requirement already satisfied: scipy in /usr/local/lib/python3.7/dist-packages (from deepchem) (1.4.1)
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Collecting rdkit-pypi
Downloading rdkit_pypi-2021.9.4-cp37-cp37m-manylinux_2_17_x86_64.manylinux2014_x86_64.whl (20.6 MB)
|████████████████████████████████| 20.6 MB 8.2 MB/s
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epchem) (2.8.2)
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018.9)
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pandas->deepchem) (1.15.0)
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.2)
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->deepchem) (3.1.0)
Installing collected packages: rdkit-pypi, deepchem
Successfully installed deepchem-2.6.1 rdkit-pypi-2021.9.4

Import Libraries
import torch
import torch.nn as nn

from torchdiffeq import odeint

import math
import numpy as np

import deepchem as dc
import matplotlib.pyplot as plt

Before diving into the core of this tutorial , let's first acquaint ourselves with usage of torchdiffeq. Let's solve following
differential equation .

when

The process to do it by hand is :

Let's solve it using ODE Solver called odeint from torchdiffeq

def f(t,z):
return t

z0 = torch.Tensor([0])
t = torch.linspace(0,2,100)
out = odeint(f, z0, t);

Let's plot our result .It should be a parabola (remember general equation of parabola as

plt.plot(t, out, 'go--')

plt.axes().set_aspect('equal','datalim')
plt.grid()
plt.show()
/usr/local/lib/python3.7/dist-packages/ipykernel_launcher.py:2: MatplotlibDeprecationWarning: Adding an axes usi
ng the same arguments as a previous axes currently reuses the earlier instance. In a future version, a new inst
ance will always be created and returned. Meanwhile, this warning can be suppressed, and the future behavior en
sured, by passing a unique label to each axes instance.

What is Neural Differential Equation ?

A neural differential equation is a differential equation using a neural network to parameterize the vector field. The
canonical example is a neural ordinary differential equation :

Here θ represents some vector of learnt parameters,

is any standard neural architecture and

is the solution. For many applications

will just be a simple feedforward network. Here

is the dimension.

Reference

The central idea now is to use a differential equation solver as part of a learnt differentiable computation graph (the sort
of computation graph ubiquitous to deep learning)

As simple example, suppose we observe some picture

(RGB and 32x32 pixels), and wish to classify it as a picture of a cat or as a picture of a dog.

With torchdiffeq , we can solve even complex higher order differential equations too. Following is a real world example ,
a set of differential equations that models a spring - mass damper system

with initial state t=0 , x=1

The right hand side may be regarded as a particular differentiable computation graph. The parameters may be fitted by
setting up a loss between the trajectories of the model and the observed trajectories in the data, backpropagating
through the model, and applying stochastic gradient descent.

class SystemOfEquations:

def init(self, km, p, g, r):

self.mat = torch.Tensor([[0,1,0],[-km, p, 0],[0,g,-r]])

def solve(self, t, x0, dx0, ddx0):

y0 = torch.cat([x0, dx0, ddx0])
out = odeint(self.func, y0, t)
return out

def func(self, t, y):

out = [email protected]
return out

x0 = torch.Tensor([1])
dx0 = torch.Tensor([0])
ddx0 = torch.Tensor([1])

t = torch.linspace(0, 4*np.pi, 1000)

solver = SystemOfEquations(1,6,3,2)
out = solver.solve(t, x0, dx0, ddx0)

plt.plot(t, out, 'r')

plt.axes()
plt.grid()
plt.show()

/usr/local/lib/python3.7/dist-packages/ipykernel_launcher.py:25: MatplotlibDeprecationWarning: Adding an axes us

ing the same arguments as a previous axes currently reuses the earlier instance. In a future version, a new ins
tance will always be created and returned. Meanwhile, this warning can be suppressed, and the future behavior e
nsured, by passing a unique label to each axes instance.

This is precisely the same procedure as the more general neural ODEs we introduced earlier. At first glance, the NDE
approach of ‘putting a neural network in a differential equation’ may seem unusual, but it is actually in line with
standard practice. All that has happened is to change the parameterisation of the vector field.

Model
Let us have a look at how to embed an ODEsolver in a neural network .

from torchdiffeq import odeint_adjoint as odeadj

class f(nn.Module):
def __init__(self, dim):
super(f, self).__init__()
self.model = nn.Sequential(
nn.Linear(dim,124),
nn.ReLU(),
nn.Linear(124,124),
nn.ReLU(),
nn.Linear(124,dim),
nn.Tanh()
)

def forward(self, t, x):

return self.model(x)
function f in above code cell , is wrapped in an nn.Module (see codecell below) thus forming the dynamics of

embedded within a neural Network. ODE Block treats the received input x as the initial value of the differential equation.
The integration interval of ODE Block is fixed at [0, 1]. And it returns the output of the layer at

class ODEBlock(nn.Module):

# This is ODEBlock. Think of it as a wrapper over ODE Solver , so as to easily connect it with our neurons !

def init(self, f):

super(ODEBlock, self).__init__()
self.f = f
self.integration_time = torch.Tensor([0,1]).float()

def forward(self, x):

self.integration_time = self.integration_time.type_as(x)
out = odeadj(
self.f,
x,
self.integration_time
)

return out[1]

class ODENet(nn.Module):

#This is our main neural network that uses ODEBlock within a sequential module

def init(self, in_dim, mid_dim, out_dim):

super(ODENet, self).__init__()
fx = f(dim=mid_dim)
self.fc1 = nn.Linear(in_dim, mid_dim)
self.relu1 = nn.ReLU(inplace=True)
self.norm1 = nn.BatchNorm1d(mid_dim)
self.ode_block = ODEBlock(fx)
self.dropout = nn.Dropout(0.4)
self.norm2 = nn.BatchNorm1d(mid_dim)
self.fc2 = nn.Linear(mid_dim, out_dim)

def forward(self, x):

batch_size = x.shape[0]
x = x.view(batch_size, -1)

out = self.fc1(x)
out = self.relu1(out)
out = self.norm1(out)
out = self.ode_block(out)
out = self.norm2(out)
out = self.dropout(out)
out = self.fc2(out)

return out

As mentioned before , Neural ODE Networks acts similar (has advantages though) to other neural networks , so we can
solve any problem with them as the existing models do. We are gonna reuse the training process mentioned in this
deepchem tutorial.

So Rather than demonstrating how to use NeuralODE model with a normal dataset, we shall use the Delaney solubility
dataset provided under deepchem . Our model will learn to predict the solubilities of molecules based on their
extended-connectivity fingerprints (ECFPs) . For performance metrics we use pearson_r2_score . Here loss is computed
directly from the model's output

tasks, dataset, transformers = dc.molnet.load_delaney(featurizer='ECFP', splitter='random')

train_set, valid_set, test_set = dataset
metric = dc.metrics.Metric(dc.metrics.pearson_r2_score)

Time to Train
We train our model for 50 epochs, with L2 as Loss Function.

# Like mentioned before one can use GPUs with PyTorch and torchdiffeq
device = torch.device("cuda" if torch.cuda.is_available() else "cpu")
model = ODENet(in_dim=1024, mid_dim=1000, out_dim=1).to(device)
model = dc.models.TorchModel(model, dc.models.losses.L2Loss())

model.fit(train_set, nb_epoch=50)

print('Training set score : ', model.evaluate(train_set,[metric]))

print('Test set score : ', model.evaluate(test_set,[metric]))

Training set score : {'pearson_r2_score': 0.9708644701066554}

Test set score : {'pearson_r2_score': 0.7104556551957734}

Neural ODEs are invertible neural nets Reference Invertible neural networks have been a significant thread of research
in the ICML community for several years. Such transformations can offer a range of unique benefits:

They preserve information, allowing perfect reconstruction (up to numerical limits) and obviating the need to store
hidden activations in memory for backpropagation.
They are often designed to track the changes in probability density that applying the transformation induces (as in
normalizing flows).
Like autoregressive models, normalizing flows can be powerful generative models which allow exact likelihood
computations; with the right architecture, they can also allow for much cheaper sampling than autoregressive
models.

While many researchers are aware of these topics and intrigued by several high-profile papers, few are familiar enough
with the technical details to easily follow new developments and contribute. Many may also be unaware of the wide
range of applications of invertible neural networks, beyond generative modelling and variational inference.

Congratulations! Time to join the Community!

Star DeepChem on GitHub

This helps build awareness of the DeepChem project and the tools for open source drug discovery that we're trying to
build.

Join the DeepChem Discord

The DeepChem Discord hosts a number of scientists, developers, and enthusiasts interested in deep learning for the life
sciences. Join the conversation!
Differentiation Infrastructure in Deepchem
Author : Rakshit Kr. Singh : Website : LinkedIn : GitHub

Scientific advancement in machine learning hinges on the effective resolution of complex optimization problems. From
material property design to drug discovery, these problems often involve numerous variables and intricate relationships.
Traditional optimization techniques often face hurdles when addressing such challenges, often resulting in slow
convergence or solutions deemed unreliable. We introduce solutions that are differentiable and also seamlessly
integrable into machine learning systems, offering a novel approach to resolving these complexities.

This tutorials introduces DeepChem's comprehensive set of differentiable optimisation tools to empower researchers
across the physical sciences. DeepChem addresses limitations of conventional methods by offering a diverse set of
optimization algorithms. These includes established techniques like Broyden's first and second methods alongside
cutting-edge advancements, allowing researchers to select the most effective approach for their specific problem.

Overview of Differentiation Utilities in Deepchem

DeepChem provides a number of optimisation algorithms and Utilities for implementing more algorithms. Some of the
optimisation algorithms provided by DeepChem are:

Broyden's First Method

Broyden's Second Method
Anderson Acceleration
Gradient Descent
Adam

Along with these optimisation algorithms, DeepChem also provides a number of utilities for implementing more
algorithms.

What are Non Linear Equations? and why do they matter?

Nonlinear equations are mathematical expressions where the relationship between the variables is not linear. Unlike
linear equations, which have a constant rate of change, nonlinear equations involve terms with higher powers or
functions like exponentials, logarithms, trigonometric functions, etc.

Nonlinear equations are essential across various disciplines, including physics, engineering, economics, biology, and
finance. They describe complex relationships and phenomena that cannot be adequately modeled with linear equations.
From gravitational interactions in celestial bodies to biochemical reactions in living organisms, non-linear equations play
a vital role in understanding and predicting real-world systems. Whether it's optimizing structures, analyzing market
dynamics, or designing machine learning algorithms.

Some Simple Non Linear Equations:

, is a trigonometric function defined for all real numbers. It represents the ratio of the length of the side opposite an
angle in a right triangle to the length of the hypotenuse.

, is an another trigonometric function. It represents the ratio of the length of the adjacent side of a right triangle to the
length of the hypotenuse when x is the measure of an acute angle.

, is a parabola, symmetric around the y-axis, with its vertex at the origin. It represents a mathematical model of
quadratic growth or decay. In physical systems, it often describes phenomena where the rate of change is proportional
to the square of the quantity involved.

import matplotlib.pyplot as plt

import numpy as np

x = np.linspace(0, 10, 100)

y1 = np.sin(x)
y2 = np.cos(x)
y3 = x**2

fig, axs = plt.subplots(1, 3, figsize=(9, 3))

axs[0].plot(x, y1, color='blue')

axs[0].set_title('Sin')

axs[1].plot(x, y2, color='red')

axs[1].set_title('Cos')

axs[2].plot(x, y3, color='green')

axs[2].set_title('x^2')

plt.tight_layout()

plt.show()

Root Finder Methods

deepchem.utils.differentiation_utils.optimize.rootfinder provides a collection of algorithms for solving
nonlinear equations. These methods are designed to find the roots of functions efficiently, making them indispensable
for a wide range of applications in mathematics, physics, engineering, and other fields.

At its core, rootfinding seeks to determine the solutions (roots) of equations, where a function equals zero. This
operation plays a pivotal role in numerous real-world applications, making it indispensable in both theoretical and
practical domains.

Broyden's First Method:

Broyden's First Method is an iterative numerical method used for solving systems of nonlinear equations. It's particularly
useful when the Jacobian matrix (the matrix of partial derivatives of the equations) is difficult or expensive to compute.

Broyden's Method is an extension of the Secant Method for systems of nonlinear equations. It iteratively updates an
approximation to the Jacobian matrix using the information from previous iterations. The algorithm converges to the
solution by updating the variables in the direction that minimizes the norm of the system of equations.

Steps:

1. Initialize the approximation to the Jacobian matrix.

2. Initialize the variables.

3. Compute the function values.

4. Update the variables.

5. Compute the change in variables.

6. Compute the function values.

7. Update the approximation to the Jacobian matrix.

8. Repeat steps 4-7 until convergence criteria are met.

References:
[1] "A class of methods for solving nonlinear simultaneous equations" by Charles G. Broyden

import torch
from deepchem.utils.differentiation_utils import rootfinder
def func1(y, A):
return torch.tanh(A @ y + 0.1) + y / 2.0
A = torch.tensor([[1.1, 0.4], [0.3, 0.8]]).requires_grad_()
y0 = torch.zeros((2,1))

# Broyden's First Method

yroot = rootfinder(func1, y0, params=(A,), method='broyden1')
print("Root By Broyden's First Method:")
print(yroot)
print("Function Value at Calculated Root:")
print(func1(yroot, A))

Root By Broyden's First Method:

tensor([[-0.0459],
[-0.0663]], grad_fn=<_RootFinderBackward>)
Function Value at Calculated Root:
tensor([[1.1735e-07],
[1.7881e-07]], grad_fn=<AddBackward0>)

from deepchem.utils.differentiation_utils.optimize.rootsolver import broyden1

def fcn(x):
return x**2 - 4 + torch.tan(x)
x0 = torch.tensor(0.0, requires_grad=True)
x = broyden1(fcn, x0)
x, fcn(x)

(tensor(2.2752, grad_fn=<ViewBackward0>),
tensor(1.7881e-06, grad_fn=<AddBackward0>))

Broyden's Second Method:

Broyden's Second Method differs from the first method in how it updates the approximation to the Jacobian matrix.
Instead of using the change in variables and function values, it uses the change in the residuals (the difference between
the function values and the target values) to update the Jacobian matrix. This approach can be more stable and robust
in certain situations.

Steps:

1...6 are same as Broyden's First Method.

7. Update the approximation to the Jacobian matrix.

8. Repeat steps 4-7 until convergence criteria are met.

# Broyden's Second Method

yroot = rootfinder(func1, y0, params=(A,), method='broyden2')

print("\nRoot by Broyden's Second Method:")
print(yroot)
print("Function Value at Calculated Root:")
print(func1(yroot, A))

Root by Broyden's Second Method:

tensor([[-0.0459],
[-0.0663]], grad_fn=<_RootFinderBackward>)
Function Value at Calculated Root:
tensor([[ 1.0300e-06],
[-3.2783e-07]], grad_fn=<AddBackward0>)
Equilibrium Methods (Fixed Point Iteration)
deepchem.utils.differentiation_utils.optimize.equilibrium contains algorithms for solving equilibrium
problems, where the goal is to find a fixed point of a function. While all the rootfinding methods can be used to solve
equilibrium problems, these specialized algorithms are designed to exploit the structure of equilibrium problems for
more efficient convergence.

Equilibrium methods are essential in machine learning for optimizing models, ensuring stability and convergence,
regularizing parameters, and analyzing strategic interactions in multi-agent systems. By leveraging equilibrium
principles and techniques, machine learning practitioners can train more robust and generalizable models capable of
addressing a wide range of real-world challenges.

The Fixed-Point Problem:

Given the function

, compute a fixed-point

such that

Classical Approach:
Steps:

1. Initialize the variables.

2. Compute the function values.

3. Update the variables.

4. Repeat steps 2-3 until convergence criteria are met.

Anderson Acceleration Approach (Anderson Mixing):

Anderson Acceleration is an iterative method for accelerating the convergence of fixed-point iterations. It combines
information from previous iterations to construct a better approximation to the fixed-point. The algorithm uses a history
of function values and updates to compute a new iterate that minimizes the residual norm.

Steps:

, fixed-point mapping

2. Choose

(e.g.,

for some integer

).
Select weights

based on the last

iterations satisfying

.
3.
import torch
import matplotlib.pyplot as plt
from deepchem.utils.differentiation_utils.optimize.equilibrium import anderson_acc
x_value, f_value = [], []
def fcn(x, a):
x_value.append(x.item())
f_value.append((a/x + x).item()/2)
return (a/x + x)/2
a = 2.0
x0 = torch.tensor([1.0], requires_grad=True)
x = anderson_acc(fcn, x0, params=[a], maxiter=16)
print("Root by Anderson Acceleration:", x.item())
print("Function Value at Calculated Root:", fcn(x, a).item())

# Plotting the convergence of Anderson Acceleration

plt.plot(x_value, label='Input Value')
plt.plot(f_value, label='Func. Value by Anderson Acce.')
plt.legend(loc='lower right')
plt.xlabel('Iteration')
plt.ylabel('Function Value')
plt.title('Convergence of Anderson Acceleration')
plt.show()

Root by Anderson Acceleration: 1.4142135381698608

Function Value at Calculated Root: 1.4142135381698608

Minimizer
deepchem.utils.differentiation_utils.optimize.minimizer provides a collection of algorithms for minimizing
functions. These methods are designed to find the minimum of a function efficiently, making them indispensable for a
wide range of applications in mathematics, physics, engineering, and other fields.

Minimization algorithms, including variants of gradient descent like ADAM, are fundamental tools in various fields of
science, engineering, and optimization.

Gradient Descent
Gradient descent is a method for unconstrained mathematical optimization. It is a first-order iterative algorithm for
finding a local minimum of a differentiable multivariate function.

It is used to minimize the cost function in various machine learning and optimization problems. It iteratively updates the
parameters in the direction of the negative gradient of the cost function.

Steps:

Denote the parameter vector to be optimized -

and

represent the initial guess.

Calculate the gradient of the cost function

with respect to each parameter.

Adjust the parameters in the opposite direction of the gradient to minimize the cost function according to the
learning rate

Steps 2 and 3 until the algorithm converges or Stops.

import torch
from deepchem.utils.differentiation_utils.optimize.minimizer import gd
def fcn(x):
return 2 * x + (x - 2) ** 2, 2 * (x - 2) + 2
x0 = torch.tensor(0.0, requires_grad=True)
x = gd(fcn, x0, [])
print("Minimum by Gradient Descent:", x.item())
print("Function Value at Calculated Minimum:", fcn(x)[0].item())

Minimum by Gradient Descent: 0.9973406791687012

Function Value at Calculated Minimum: (tensor(3.0000), tensor(-0.0053))

ADAM (Adaptive Moment Estimation)

ADAM is an optimization algorithm used for training deep learning models. It's an extension of the gradient descent
optimization algorithm and combines the ideas of both momentum and RMSProp algorithms.

Steps:

ADAM initializes two moving average variables:

(the first moment, similar to momentum) and

(the second moment, similar to RMSProp).

At each iteration of training, the gradients of the parameters concerning the loss function are computed.

The moving averages

and

are updated using exponential decay, with momentum and RMSProp components respectively:

Due to the initialization of the moving averages to zero vectors, there's a bias towards zero, especially during the
initial iterations. To correct this bias, ADAM applies a bias correction step:
5.

Finally, the parameters (weights and biases) of the model are updated using the moving averages and the learning
rate

import torch
from deepchem.utils.differentiation_utils.optimize.minimizer import adam
def fcn(x):
return 2 * x + (x - 2) ** 2, 2 * (x - 2) + 2
x0 = torch.tensor(10.0, requires_grad=True)
x = adam(fcn, x0, [], maxiter=20000)
print("X at Minimum by Adam:", x.item())
print("Function Value at Calculated Minimum:", fcn(x)[0].item())

X at Minimum by Adam: 1.0067708492279053

Function Value at Calculated Minimum: 3.0000457763671875

Conclusion
Differentiable optimization techniques are essential for many advanced computational experiments involving
Environment Simulations like DFT, Physics Informed Neural Networks and as fundamental mathematical foundation for
Molecular Simulation like Monte Carlo and Molecular Dynamics.

By integrating deep learning into simulations, we optimize efficiency and accuracy by leveraging trainable neural
networks to replace costly or less precise components. This advancement holds immense potential for expediting
scientific advancements and addressing longstanding mysteries with greater efficacy.

References
[1] Raissi M, Perdikaris P, Karniadakis GE. Physics-informed neural networks: A deep learning framework for solving
forward and inverse problems involving nonlinear partial differential equations. Journal of Computational physics (2019)

[2] Muhammad F. Kasim, Sam M. Vinko. Learning the exchange-correlation functional from nature with fully
differentiable density functional theory. 2021 American Physical Society

[3] Nathan Argaman, Guy Makov. Density Functional Theory -- an introduction. American Journal of Physics 68 (2000),
69-79

[4] John Ingraham et al. Learning Protein Structure with a Differentiable Simulator. ICLR. 2019.

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Quantum Chemistry,
title={Differentiation Infrastructure in Deepchem},
organization={DeepChem},
author={Singh, Rakshit kr.},
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/Differentiation_Infrastructure_in_D

year={2024},
}

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Ordinary Differential Equation Solving
Author : Rakshit Kr. Singh : Website : LinkedIn : GitHub

Ordinary Differential Equations (ODEs) are a cornerstone of mathematical modeling, essential for understanding
dynamic systems in scientific and engineering fields.

This tutorial aims to introduce you to ODE solving tools in DeepChem.

What are Ordinary Differential Equations?

An ordinary differential equation (ODE) is a type of differential equation that depends on a single independent variable.
In contrast to partial differential equations (PDEs), which involve multiple independent variables, ODEs focus on
relationships where changes occur with respect to just one variable. The term "ordinary" distinguishes these equations
from stochastic differential equations (SDEs), which incorporate random processes.

ODEs consist of unknown functions and their derivatives, establishing relationships that describe how a quantity
changes over time or space. These equations are fundamental in expressing the dynamics of systems.

General Form of an ODE -

Here,

is the derivative of

with regards to

, and

is a function of

and

Why we should Care About Ordinary Differential Equations

They are essential because they model how physical quantities change over time. ODEs are used in:

Physics: To describe the motion of particles, the evolution of wave functions, and more.

Engineering: To design control systems, signal processing, and electrical circuits.

Biology: To model population dynamics, the spread of diseases, and biological processes.

Economics: To analyze growth models, market equilibrium, and financial systems.

Control Systems and Robotics: In control systems and robotics, ODEs are fundamental in describing the dynamics of
systems.

Solving Ordinary Differential Equations

Steps:

Formulate the ODE: An ODE involves an unknown function

and its derivatives.

Find the general solution: The goal is to find the function

that satisfies the ODE. This process often involves integration.

Apply initial or boundary condition: To find a specific solution, you often need additional information, such as the
value of the function and its derivatives at certain points. These are called initial or boundary conditions.

Methods for Solving ODEs in DeepChem

DeepChem boasts a number of methods for solving ODEs. Some of them are:

Euler's Method
Mid Point Method
3/8 Method
RK-4 Method

Euler's Method (1st Order Runge-Kutta Method)

It is the simplest Runge–Kutta method
Explicit Runge–Kutta method with one stage

Mid-Point Method (2nd Order Runge-Kutta Method)

It is also called modified Euler's method
second-order method with two stages

from deepchem.utils.differentiation_utils.integrate.explicit_rk import mid_point_ivp, fwd_euler_ivp

import matplotlib.pyplot as plt
import torch

# Simple ODE dy/dt = a*y

def ode(t, y, params):
a = params[0]
return y * a

t = torch.linspace(0, 20, 5)
y_0 = torch.tensor([1])
a = torch.tensor([1])

sol_fwd_euler = fwd_euler_ivp(ode, y_0, t, [a])

sol_mid_point = mid_point_ivp(ode, y_0, t, [a])

plt.plot(t, sol_fwd_euler, "-b", label="Euler's method")

plt.plot(t, sol_mid_point, "-r", label="Mid-point method")
plt.legend(loc="upper left")
plt.show()

No normalization for SPS. Feature removed!

No normalization for AvgIpc. Feature removed!
Skipped loading some Tensorflow models, missing a dependency. No module named 'tensorflow'
Skipped loading modules with pytorch-geometric dependency, missing a dependency. No module named 'dgl'
Skipped loading modules with transformers dependency. No module named 'transformers'
cannot import name 'HuggingFaceModel' from 'deepchem.models.torch_models' (/home/gigavolt/deepchem/deepchem/mode
ls/torch_models/__init__.py)
Skipped loading modules with pytorch-lightning dependency, missing a dependency. No module named 'lightning'
Skipped loading some Jax models, missing a dependency. No module named 'jax'
Skipped loading some PyTorch models, missing a dependency. No module named 'tensorflow'
RK4 Method

for n = 0, 1, 2, 3, ...

Second Order Differential Equation

Example:

given,

and

at t=0 is -5

Procedure:
from deepchem.utils.differentiation_utils.integrate.explicit_rk import rk4_ivp
import matplotlib.pyplot as plt
import torch

def sode(variables, t, params):

y, z = variables

a = params[0]

dydt = z
dzdt = a * y - z

return torch.tensor([dydt, dzdt])

params = torch.tensor([6])
t = torch.linspace(0, 1, 100)
y0 = torch.tensor([5, -5])
sol = rk4_ivp(sode, y0, t, params)

plt.plot(t, sol[:, 0])

plt.show()

Comparing with Particular Solution

Particular Solution:

yy = 2 * torch.exp(2 * t) + 3 * torch.exp(-3 * t)

plt.plot(t, yy, "-b", label="Known solution")

plt.plot(t, sol[:, 0], "-r", label="RK4 method")
plt.legend(loc="upper left")
plt.show()
Solving Lotka Volterra using Deepchem
The Lotka–Volterra equations, also known as the Lotka–Volterra predator–prey model, are a pair of first-order nonlinear
differential equations, frequently used to describe the dynamics of biological systems in which two species interact, one
as a predator and the other as prey. The populations change through time according to the pair of equations:

The Lotka–Volterra system of equations is an example of a Kolmogorov model, which is a more general framework that
can model the dynamics of ecological systems with predator–prey interactions, competition, disease, and mutualism.

from deepchem.utils.differentiation_utils.integrate.explicit_rk import rk38_ivp

import matplotlib.pyplot as plt
import torch

def lotka_volterra(y, x, params):

y1, y2 = y
a, b, c, d = params
return torch.tensor([(a * y1 - b * y1 * y2), (c * y2 * y1 - d * y2)])

t = torch.linspace(0, 50, 10000)

solver_param = [lotka_volterra,
torch.tensor([10., 1.]),
t,
torch.tensor([1.1, 0.4, 0.1, 0.4])]

sol_rk38 = rk38_ivp(*solver_param)

plt.plot(t, sol_rk38)

plt.show()
lotka volterra (Parammeter Estimation)
Parameter Estimation is used to estimate the values of the changable parameters in the ODE. The parameters describe
an underlying physical setting in such a way that their value affects the distribution of the measured data. An estimator
attempts to approximate the unknown parameters using the measurements.

import pandas as pd

dataset = pd.read_csv('assets/population_data.csv')
years = torch.tensor(dataset['year'])
fish_pop = torch.tensor(dataset['fish_hundreds'])
bears_pop = torch.tensor(dataset['bears_hundreds'])

plt.plot(fish_pop, "-b", label="Fish population")

plt.plot(bears_pop, "-r", label="Bear population")
plt.legend(loc="upper left")
plt.title("Population data")
plt.show()

from deepchem.utils.differentiation_utils.integrate.explicit_rk import rk4_ivp

import torch
import matplotlib.pyplot as plt

def lotka_volterra(y, x, params):

y1, y2 = y
a, b, c, d = params

return torch.tensor([a * y1 - b * y1 * y2, c * y2 * y1 - d * y2])

def loss_function(params, years,fish_pop, bears_pop):

y0 = torch.tensor([fish_pop[0], bears_pop[0]])

t = torch.linspace(years[0], years[-1], len(years))

output = rk4_ivp(lotka_volterra, y0, t, params)

loss = 0

for i in range(len(years)):
data_fish = fish_pop[i]
model_fish = output[i,0]

data_bears = bears_pop[i]
model_bears = output[i,1]

res = (data_fish - model_fish)2 + (data_bears - model_bears)2

loss += res

return(loss)

import scipy.optimize

params0 = torch.tensor([1.1, .4, .1, .4])

minimum = scipy.optimize.fmin(loss_function, params0, args=(years,fish_pop, bears_pop))

alpha_fit = minimum[0]
beta_fit = minimum[1]
delta_fit = minimum[2]
gamma_fit = minimum[3]

params = torch.tensor([alpha_fit, beta_fit, delta_fit, gamma_fit])

y0 = torch.tensor([fish_pop[0], bears_pop[0]])

t = torch.linspace(years[0], years[-1], 1000)

output = rk4_ivp(lotka_volterra, y0, t, params)

plt.plot(t, output)
plt.show()

Optimization terminated successfully.

Current function value: 42.135876
Iterations: 155
Function evaluations: 256

SIR Epidemiology
The SIR model is one of the simplest compartmental models, and many models are derivatives of this basic form. The
model consists of three compartments:

S: The number of susceptible individuals. When a susceptible and an infectious individual come into "infectious
contact", the susceptible individual contracts the disease and transitions to the infectious compartment.
I: The number of infectious individuals. These are individuals who have been infected and are capable of infecting
susceptible individuals.
R: The number of removed (and immune) or deceased individuals. These are individuals who have been infected
and have either recovered from the disease and entered the removed compartment, or died. It is assumed that the
number of deaths is negligible with respect to the total population. This compartment may also be called
"recovered" or "resistant".

import torch
import matplotlib.pyplot as plt
from deepchem.utils.differentiation_utils.integrate.explicit_rk import rk4_ivp

def sim(variables, t, params):

S, I, R = variables

N = S + I + R

beta, gamma = params

dSdt = - beta * I * S / N
dIdt = beta * I * S / N - gamma * I
dRdt = gamma * I

return torch.tensor([dSdt, dIdt, dRdt])

t = torch.linspace(0, 500, 1000)

beta = 0.04
gamma = 0.01

params = torch.tensor([beta, gamma])

y0 = torch.tensor([100, 1, 0])

y = rk4_ivp(sim, y0, t, params)

plt.plot(t, y)
plt.legend(["Susceptible", "Infectious", "Removed"])
plt.show()
SIS Model
Some infections, for example, those from the common cold and influenza, do not confer any long-lasting immunity. Such
infections may give temporary resistance but do not give long-term immunity upon recovery from infection, and
individuals become susceptible again.

Model:

Total Population:

import torch
import matplotlib.pyplot as plt
from deepchem.utils.differentiation_utils.integrate.explicit_rk import rk4_ivp

def sim(variables, t, params):

S, I = variables

N = S + I

beta, gamma = params

dSdt = - beta * I * S / N + gamma * I

dIdt = beta * I * S / N - gamma * I

return torch.tensor([dSdt, dIdt])

t = torch.linspace(0, 500, 1000)

beta = 0.04
gamma = 0.01

params = torch.tensor([beta, gamma])

y0 = torch.tensor([100, 1])

y = rk4_ivp(sim, y0, t, params)

plt.plot(t, y)
plt.legend(["Susceptible", "Infectious"])
plt.show()
References
1. More Computational Biology and Python by Mike Saint-Antoine https://www.youtube.com/playlist?
list=PLWVKUEZ25V97W2qS7faggHrv5gdhPcgjq

2. Compartmental models in epidemiology. (2024, May 27). In Wikipedia.

https://en.wikipedia.org/wiki/Compartmental_models_in_epidemiology

3. Runge–Kutta methods. (2024, June 1). In Wikipedia. https://en.wikipedia.org/wiki/Runge%E2%80%93Kutta_methods

Citing This Tutorial

If you found this tutorial useful please consider citing it using the provided BibTeX.

@manual{Differential Equation,
title={Differentiation Infrastructure in Deepchem},
organization={DeepChem},
author={Singh, Rakshit kr. and Ramsundar, Bharath},
howpublished =
{\url{https://github.com/deepchem/deepchem/blob/master/examples/tutorials/ODE_Solving.ipynb}},
year={2024},
}

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Introduction To Equivariance and Equivariant Modeling
Table of Contents:
Introduction
What is Equivariance
Why Do We Need Equivariance
Example
References

Introduction
In the preceding sections of this tutorial series, we focused on training models using DeepChem for various applications.
However, we haven't yet addressed the important topic of equivariant modeling.

Equivariant modeling ensures that the relationship between input and output remains consistent even when subjected
to symmetry operations. By incorporating equivariant modeling techniques, we can effectively analyze and predict
diverse properties by leveraging the inherent symmetries present in the data. This is particularly valuable in the fields of
cheminformatics, bioinformatics, and material sciences, where understanding the interplay between symmetries and
properties of molecules and materials is critical.

This tutorial aims to explore the concept of equivariance and its significance within the domains of chemistry, biology,
and material sciences. We will delve into the reasons why equivariant modeling is vital for accurately characterizing and
predicting the properties of molecules and materials. By the end, you will have a solid understanding of the importance
of equivariance and how it can significantly enhance our modeling capabilities in these areas.

You can follow this tutorial using the Google Colab. If you'd like to open this notebook in colab, you can use the following
link.

Open in Colab

What is Equivariance
A key aspect of the structure in our data is the presence of certain symmetries. To effectively capture this structure, our
model should incorporate our knowledge of these symmetries.Therefore, our model should retain the symmetries of the
input data in its outputs. In other words, when we apply a symmetry operation (denoted by σ) to the input and pass it
through the model, the result should be the same as applying σ to the output of the model.

Mathematically, we can express this idea as an equation:

f(σ(x)) = σ(f(x))

Here, f represents the function learned by our model. If this equation holds for every symmetry operation in a collection
S, we say that f is equivariant with respect to S.

While a precise definition of equivariance involves group theory and allows for differences between the applied
symmetry operations on the input and output, we'll focus on the case where they are identical to keep things simpler.
Group Equivariant Convolutional Networks exemplify this stricter definition of equivariance.

Interestingly, equivariance shares a similarity with linearity. Just as linear functions are equivariant with respect to
scalar multiplication, equivariant functions allow symmetry operations to be applied inside or outside the function.

To gain a better understanding, let's consider Convolutional Neural Networks (CNNs). The image below demonstrates
how CNNs exhibit equivariance with respect to translation: a shift in the input image directly corresponds to a shift in
the output features.
It is also useful to relate equivariance to the concept of invariance, which is more familiar. If a function f is invariant, its
output remains unchanged when σ is applied to the input. In this case, the equation simplifies to:

f(σ(x)) = f(x)

An equivariant embedding in one layer can be transformed into an invariant embedding in a subsequent layer. The
feasibility and meaningfulness of this transformation depend on the implementation of equivariance. Notably, networks
with multiple convolutional layers followed by a global average pooling layer (GAP) achieve this conversion. In such
cases, everything up to the GAP layer exhibits translation equivariance, while the output of the GAP layer (and the entire
network) becomes invariant to translations of the input.

Why Do We Need Equivariance

Equivariance is a critical concept in modeling various types of data, particularly when dealing with structures and
symmetries. It provides a powerful framework for capturing and leveraging the inherent properties and relationships
present in the data. In this section, we will explore the reasons why equivariance is essential and how it is particularly
advantageous when working with graph-structured data.

1. Preserving Structural Information

Data often exhibits inherent structural properties and symmetries. Equivariant models preserve the structural
information present in the data, allowing us to analyze and manipulate it while maintaining consistency under symmetry
operations. By doing so, equivariant models capture the underlying relationships and patterns, leading to more accurate
and meaningful insights.

2. Handling Symmetry and Invariance

Symmetries and invariances are prevalent in many real-world systems. Equivariant models ensure that the learned
representations and predictions are consistent under these symmetries and invariances. By explicitly modeling
equivariance, we can effectively handle and exploit these properties, leading to robust and reliable models.

3. Improved Generalization
Equivariant models have the advantage of generalizing well to unseen data. By incorporating the known symmetries
and structures of the domain into the model architecture, equivariance ensures that the model can effectively capture
and utilize these patterns even when presented with novel examples. This leads to improved generalization
performance, making equivariant models valuable in scenarios where extrapolation or prediction on unseen instances is
crucial.
4. Efficient Processing of Graph-Structured Data
Graph-structured data possess rich relational information and symmetries. Equivariant models specifically tailored for
graph data offer a natural and efficient way to model and reason about these complex relationships. By considering the
symmetries of the graph, equivariant models can effectively capture the local and global patterns, enabling tasks such
as node classification, link prediction, and graph generation.

Example
Traditional machine learning (ML) algorithms face challenges when predicting molecular properties due to the
representation of molecules. Typically, molecules are represented as 3D Cartesian arrays with a shape of (points, 3).
However, neural networks (NN) cannot directly process such arrays because each position in the array lacks individual
significance. For instance, a molecule can be represented by one Cartesian array centered at (0, 0, 0) and another
centered at (15, 15, 15), both representing the same molecule but with distinct numerical values. This exemplifies
translational variance. Similarly, rotational variance arises when the molecule is rotated instead of translated.

In these examples, if the different arrays representing the same molecule are inputted into the NN, it would perceive
them as distinct molecules, which is not the case. To address these issues of translational and rotational variance,
considerable efforts have been devoted to devising alternative input representations for molecules. Let’s demonstrate
with some code how to go about creating functions that obey set of equivariances. We won’t be training these models
because training has no effect on equivariances.

To define the molecule, we represent it as a collection of coordinates (denoted as

) and corresponding features (denoted as

). The features are encoded as one-hot vectors, where [1, 0] indicates a carbon atom, and [0, 1] indicates a hydrogen
atom. In this specific example, our focus is on predicting the energy associated with the molecule. It's important to note
that we will not be training our models, meaning the predicted energy values will not be accurate.

Let's define a random molecule with 12 atoms as an example:

import numpy as np
np.random.seed(42) # seed for reproducibility

R_i = np.random.rand(12, 3) # 12 atoms with xyz coordinates

N = R_i.shape[0] # number of atoms
X_i = np.zeros((N, 2)) # feature vectors for the atoms with shape (N, 2)
X_i[:4, 0] = 1
X_i[4:, 1] = 1

An example of a model that lacks equivariances is a one-hidden layer dense neural network. In this model, we
concatenate the positions and features of our data into a single input tensor, which is then passed through a dense
layer. The dense layer utilizes the hyperbolic tangent (tanh) activation function and has a hidden layer dimension of 16.
The output layer, which performs regression to energy, does not have an activation function. The weights of the model
are always initialized randomly.

Let's define our hidden model and initialize the weights:

def hidden_model(r: np.ndarray, x: np.ndarray, w1: np.ndarray, w2: np.ndarray, b1: np.ndarray, b2: float) -> np.ndarr
r"""Computes the output of a 1-hidden layer neural network model.

Parameters
----------
r : np.ndarray
Input array for position values.
Shape: (num_atoms, num_positions)
x : np.ndarray
Input array for features.
Shape: (num_atoms, num_features)
w1 : np.ndarray
Weight matrix for the first layer.
Shape: (num_positions + num_features, hidden_size)
w2 : np.ndarray
Weight matrix for the second layer.
Shape: (hidden_size, output_size)
b1 : np.ndarray
Bias vector for the first layer.
Shape: (hidden_size,)
b2 : float
Bias value for the second layer.

Returns
-------
float
Predicted energy of the molecule
"""
i = np.concatenate((r, x), axis=1).flatten() # Stack inputs into one large input
v = np.tanh(i @ w1 + b1) # Apply activation function to first layer
v = v @ w2 + b2 # Multiply with weights and add bias for the second layer
return v

# Initialize weights for a network with hidden size is 16

w1 = np.random.normal(size=(N * 5, 16)) # 3(#positions) + 2(#features) = 5
b1 = np.random.normal(size=(16,))
w2 = np.random.normal(size=(16,))
b2 = np.random.normal()

Although our model is not trained, we are not concerned about. Since, we only want see if our model is affected by
permutations, translations and rotations

import scipy.spatial.transform as transform

rotate = transform.Rotation.from_euler("x", 60, degrees=True) # Rotate around x axis by 60 degrees

permuted_R_i = np.copy(R_i)
permuted_R_i[0], permuted_R_i[1] = R_i[1], R_i[0] # Swap the rows of R_i

print("without change:", hidden_model(R_i, X_i, w1, w2, b1, b2))

print("after permutation:", hidden_model(permuted_R_i, X_i, w1, w2, b1, b2))
print("after translation:", hidden_model(R_i + np.array([3, 3, 3]), X_i, w1, w2, b1, b2))
print("after rotation:", hidden_model(rotate.apply(R_i), X_i, w1, w2, b1, b2))

without change: 9.945112980229641

after permutation: 9.461406567572851
after translation: 5.963826685170721
after rotation: 7.191211524244547

As expected, our model is not invariant to any permutations, translations, or rotations. Let's fix them.

Permutational Invariance
In a molecular context, the arrangement or ordering of points in an input tensor holds no significance. Therefore, it is
crucial to be cautious and avoid relying on this ordering. To ensure this, we adopt a strategy of solely performing atom-
wise operations within the network to obtain atomic property predictions. When predicting molecular properties, we
need to cumulatively combine these atomic predictions, such as using summation, to arrive at the desired result. This
approach guarantees that the model does not depend on the arbitrary ordering of atoms within the input tensor.

Let's fix permutation invariance problem exists in our hidden model.

def hidden_model_perm(r: np.ndarray, x: np.ndarray, w1: np.ndarray, w2: np.ndarray, b1: np.ndarray, b2: float) -> np
r"""Computes the output of a 1-hidden layer neural network model with permutation invariance.

Returns
-------
float
Predicted energy of the molecule
"""
i = np.concatenate((r, x), axis=1) # Stack inputs into one large input
v = np.tanh(i @ w1 + b1) # Apply activation function to first layer
v = np.sum(v, axis=0) # Reduce the output by summing across the axis which gives permutational invariance
v = v @ w2 + b2 # Multiply with weights and add bias for the second layer
return v
# Initialize weights
w1 = np.random.normal(size=(5, 16))
b1 = np.random.normal(size=(16,))
w2 = np.random.normal(size=(16,))
b2 = np.random.normal()

In the original implementation, the model computes intermediate activations v for each input position separately and
then concatenates them along the axis 0. By summing across axis 0 with (np.sum(v, axis=0)), the model effectively
collapses all the intermediate activations into a single vector, regardless of the order of the input positions.

This reduction operation allows the model to be permutation invariant because the final output is only dependent on the
aggregated information from the intermediate activations and is not affected by the specific order of the input positions.
Therefore, the model produces the same output for different permutations of the input positions, ensuring permutation
invariance.

Now let's see if this changes affected our model's sensitivity to permutations.

print("without change:", hidden_model_perm(R_i, X_i, w1, w2, b1, b2))

print("after permutation:", hidden_model_perm(permuted_R_i, X_i, w1, w2, b1, b2))
print("after translation:", hidden_model_perm(R_i + np.array([3, 3, 3]), X_i, w1, w2, b1, b2))
print("after rotation:", hidden_model_perm(rotate.apply(R_i), X_i, w1, w2, b1, b2))

without change: -19.370847873678944

after permutation: -19.370847873678944
after translation: -67.71502903638384
after rotation: 5.311140035302996

Indeed! As anticipated, our model demonstrates invariance to permutations while remaining sensitive to translations or
rotations.

Translational Invariance
To address the issue of translational variance in modeling molecules, one approach is to compute the distance matrix of
the molecule. This distance matrix provides a representation that is invariant to translation. However, this approach
introduces a challenge as the distance features change from having three features per atom to

features per atom. Consequently, we have introduced a dependency on the number of atoms in our distance features,
making it easier to inadvertently break permutation invariance. To mitigate this issue, we can simply sum over the
newly added axis, effectively collapsing the information into a single value. This summation ensures that the model
remains invariant to permutations, restoring the desired permutation invariance property.

Let's fix translation invariance problem exists in our hidden model

def hidden_model_permute_translate(r: np.ndarray, x: np.ndarray, w1: np.ndarray, w2: np.ndarray, b1: np.ndarray, b2
r"""Computes the output of a 1-hidden layer neural network model with permutation and translation invariance.

Returns
-------
float
Predicted energy of the molecule
"""
d = r - r[:, np.newaxis] # Compute pairwise distances using broadcasting

# Stack inputs into one large input of N x N x 5

# Concatenate doesn't broadcast, so we manually broadcast the Nx2 x matrix
# into N x N x 2
i = np.concatenate((d, np.broadcast_to(x, (d.shape[:-1] + x.shape[-1:]))), axis=-1)
v = np.tanh(i @ w1 + b1) # Apply activation function to first layer

v = np.sum(v, axis=(0, 1)) # Reduce the output over both axes by summing
v = v @ w2 + b2 # Multiply with weights and add bias for the second layer
return v

To achieve translational invariance, the function calculates pairwise distances between the position values in the r
array. This is done by subtracting r from r[:, np.newaxis], which broadcasts r along a new axis, enabling element-wise
subtraction.

The pairwise distance calculation is based on the fact that subtracting the positions r from each other effectively
measures the distance or difference between them. By including the pairwise distances in the input, the model can learn
and capture the relationship between the distances and the features. This allows the model to be invariant to
translations, meaning that shifting the positions within each set while preserving their relative distances will result in the
same output.

Now let's see if this changes affected our model's sensitivity to permutations.

print("without change:", hidden_model_permute_translate(R_i, X_i, w1, w2, b1, b2))

print("after permutation:", hidden_model_permute_translate(permuted_R_i, X_i, w1, w2, b1, b2))
print("after translation:", hidden_model_permute_translate(R_i + np.array([3, 3, 3]), X_i, w1, w2, b1, b2))
print("after rotation:", hidden_model_permute_translate(rotate.apply(R_i), X_i, w1, w2, b1, b2))

without change: 193.79734623037373

after permutation: 193.79734623037385
after translation: 193.79734623037368
after rotation: 188.36773620787383

Yes! Our model is invariant to both permutations and translations but not to rotations.

Rotational Invariance
Atom-centered symmetry functions exhibit rotational invariance due to the invariance of the distance matrix. While this
property is suitable for tasks where scalar values, such as energy, are predicted from molecules, it poses a challenge for
problems that depend on directionality. In such cases, achieving rotational equivariance is desired, where the output of
the network rotates in the same manner as the input. Examples of such problems include force prediction and molecular
dynamics.

To address this, we can convert the pairwise vectors into pairwise distances. To simplify the process, we utilize squared
distances. This conversion allows us to incorporate directional information while maintaining simplicity. By considering
the squared distances, we enable the network to capture and process the relevant geometric relationships between
atoms, enabling rotational equivariance and facilitating accurate predictions for direction-dependent tasks.

def hidden_model_permute_translate_rotate(r: np.ndarray, x: np.ndarray, w1: np.ndarray, w2: np.ndarray, b1: np.ndarra
r"""Computes the output of a 1-hidden layer neural network model with permutation, translation, and rotation inva

Parameters
----------
r : np.ndarray
Input array for position values.
Shape: (num_atoms, num_positions)
x : np.ndarray
Input array for features.
Shape: (num_atoms, num_features)
w1 : np.ndarray
Weight matrix for the first layer.
Shape: (num_positions, hidden_size)
w2 : np.ndarray
Weight matrix for the second layer.
Shape: (hidden_size, output_size)
b1 : np.ndarray
Bias vector for the first layer.
Shape: (hidden_size,)
b2 : float
Bias value for the second layer.

Returns
-------
float
Predicted energy of the molecule
"""
# Compute pairwise distances using broadcasting
d = r - r[:, np.newaxis]
# Compute squared distances
d2 = np.sum(d**2, axis=-1, keepdims=True)

# Stack inputs into one large input of N x N x 3

# Concatenate doesn't broadcast, so we manually broadcast the Nx2 x matrix
# into N x N x 2
i = np.concatenate((d2, np.broadcast_to(x, (d2.shape[:-1] + x.shape[-1:]))), axis=-1)
v = np.tanh(i @ w1 + b1) # Apply activation function to first layer

# Reduce the output over both axes by summing

v = np.sum(v, axis=(0, 1))

v = v @ w2 + b2 # Multiply with weights and add bias for the second layer
return v

# Initialize weights
w1 = np.random.normal(size=(3, 16))
b1 = np.random.normal(size=(16,))
w2 = np.random.normal(size=(16,))
b2 = np.random.normal()

The hidden_model_permute_trans_rotate function achieves rotational invariance through the utilization of pairwise
squared distances between atoms, instead of the pairwise vectors themselves. By using squared distances, the function
is able to incorporate directional information while still maintaining simplicity in the calculation.

Squared distances inherently encode geometric relationships between atoms, such as their relative positions and
orientations. This information is essential for capturing the directionality of interactions and phenomena in tasks like
force prediction and molecular dynamics, where rotational equivariance is desired.

The conversion from pairwise vectors to pairwise squared distances allows the model to capture and process these
geometric relationships. Since squared distances only consider the magnitudes of vectors, disregarding their directions,
the resulting network output remains invariant under rotations of the input.

Now let's see if this changes affected our model's sensitivity to rotations.

print("without change:", hidden_model_permute_trans_rotate(R_i, X_i, w1, w2, b1, b2))

print("after permutation:", hidden_model_permute_trans_rotate(permuted_R_i, X_i, w1, w2, b1, b2))
print("after translation:", hidden_model_permute_trans_rotate(R_i + np.array([3, 3, 3]), X_i, w1, w2, b1, b2))
print("after rotation:", hidden_model_permute_trans_rotate(rotate.apply(R_i), X_i, w1, w2, b1, b2))

without change: 585.1386319324105

after permutation: 585.1386319324106
after translation: 585.1386319324105
after rotation: 585.1386319324105

Yes! Now our model is invariant to both permutations, translations, and rotations.

With these new changes, our model exhibits improved representation capacity and generalization while preserving the
symmetry of the molecules.

References
Bronstein, M.M., Bruna, J., Cohen, T., & Velivckovi'c, P. (2021). Geometric Deep Learning: Grids, Groups, Graphs,
Geodesics, and Gauges. ArXiv, abs/2104.13478.

White, A.D. (2022). Deep learning for molecules and materials. Living Journal of Computational Molecular Science.

Geiger, M., & Smidt, T.E. (2022). e3nn: Euclidean Neural Networks. ArXiv, abs/2207.09453.

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